Download PDF
Semin Liver Dis 2024; 44(03): 343-355
DOI: 10.1055/a-2404-7973
Review Article

Hepatic Extracellular Matrix and Its Role in the Regulation of Liver Phenotype

Gavin E. Arteel
1   Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
2   Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
› Author Affiliations Financial Support This work was supported, in part, by grants from NIH (R01 AA021978 and P30 DK120531).
› Further Information
    Permissions and Reprints


Abstract

The hepatic extracellular matrix (ECM) is most accurately depicted as a dynamic compartment that comprises a diverse range of players that work bidirectionally with hepatic cells to regulate overall homeostasis. Although the classic meaning of the ECM referred to only proteins directly involved in generating the ECM structure, such as collagens, proteoglycans, and glycoproteins, the definition of the ECM is now broader and includes all components associated with this compartment. The ECM is critical in mediating phenotype at the cellular, organ, and even organismal levels. The purpose of this review is to summarize the prevailing mechanisms by which ECM mediates hepatic phenotype and discuss the potential or established role of this compartment in the response to hepatic injury in the context of steatotic liver disease.

Keywords

extracellular matrix - matrisome - hepatic - liver disease


Publication History

Accepted Manuscript online:
27 August 2024

Article published online:
17 September 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Naba A, Clauser KR, Ding H, Whittaker CA, Carr SA, Hynes RO. The extracellular matrix: tools and insights for the “omics” era. Matrix Biol 2016; 49: 10-24
    CrossrefPubMedGoogle Scholar
  • 2 Naba A, Clauser KR, Hoersch S, Liu H, Carr SA, Hynes RO. The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics 2012; 11 (04) 014647
    CrossrefPubMedGoogle Scholar
  • 3 Hynes RO. The extracellular matrix: not just pretty fibrils. Science 2009; 326 (5957) 1216-1219
    CrossrefPubMedGoogle Scholar
  • 4 Arteel GE, Naba A. The liver matrisome - looking beyond collagens. JHEP Rep Innov Hepatol 2020; 2 (04) 100115
    CrossrefPubMedGoogle Scholar
  • 5 Karsdal MA, Nielsen SH, Leeming DJ. et al. The good and the bad collagens of fibrosis - their role in signaling and organ function. Adv Drug Deliv Rev 2017; 121: 43-56
    CrossrefPubMedGoogle Scholar
  • 6 Martinez-Hernandez A, Amenta PS. The hepatic extracellular matrix. I. Components and distribution in normal liver. Virchows Arch A Pathol Anat Histopathol 1993; 423 (01) 1-11
    CrossrefPubMedGoogle Scholar
  • 7 Friedman SL. Extracellular matrix. In: Dufour JF, Clavien PA. ed. Signaling Pathways in Liver Diseases. Berlin: Springer; 2010: 93-104
    Google Scholar
  • 8 Griffiths MR, Keir S, Burt AD. Basement membrane proteins in the space of Disse: a reappraisal. J Clin Pathol 1991; 44 (08) 646-648
    CrossrefPubMedGoogle Scholar
  • 9 Sun BK, Siprashvili Z, Khavari PA. Advances in skin grafting and treatment of cutaneous wounds. Science 2014; 346 (6212) 941-945
    CrossrefPubMedGoogle Scholar
  • 10 Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med 2014; 6 (265) 265sr6
    CrossrefPubMedGoogle Scholar
  • 11 Lin P, Zhang G, Li H. The role of extracellular matrix in wound healing. Dermatol Surg 2023; 49 (5S): S41-S48
    CrossrefPubMedGoogle Scholar
  • 12 Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 2014; 15 (12) 786-801
    CrossrefPubMedGoogle Scholar
  • 13 Harvey A, Montezano AC, Lopes RA, Rios F, Touyz RM. Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications. Can J Cardiol 2016; 32 (05) 659-668
    CrossrefPubMedGoogle Scholar
  • 14 Sessions AO, Engler AJ. Mechanical regulation of cardiac aging in model systems. Circ Res 2016; 118 (10) 1553-1562
    CrossrefPubMedGoogle Scholar
  • 15 Saccà SC, Gandolfi S, Bagnis A. et al. From DNA damage to functional changes of the trabecular meshwork in aging and glaucoma. Ageing Res Rev 2016; 29: 26-41
    CrossrefPubMedGoogle Scholar
  • 16 Phillip JM, Aifuwa I, Walston J, Wirtz D. The mechanobiology of aging. Annu Rev Biomed Eng 2015; 17: 113-141
    CrossrefPubMedGoogle Scholar
  • 17 Lin X, Lai Y. Scarring skin: mechanisms and therapies. Int J Mol Sci 2024; 25 (03) 25
    CrossrefPubMedGoogle Scholar
  • 18 Stone RC, Chen V, Burgess J, Pannu S, Tomic-Canic M. Genomics of human fibrotic diseases: disordered wound healing response. Int J Mol Sci 2020; 21 (22) 21
    CrossrefPubMedGoogle Scholar
  • 19 Campana L, Iredale JP. Regression of liver fibrosis. Semin Liver Dis 2017; 37 (01) 1-10
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Friedman SL. Stellate cell activation in alcoholic fibrosis – an overview. Alcohol Clin Exp Res 1999; 23 (05) 904-910
    PubMedGoogle Scholar
  • 21 Gressner OA, Weiskirchen R, Gressner AM. Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options. Comp Hepatol 2007; 6: 7
    CrossrefPubMedGoogle Scholar
  • 22 Martinez-Hernandez A, Amenta PS. The extracellular matrix in hepatic regeneration. FASEB J 1995; 9 (14) 1401-1410
    CrossrefPubMedGoogle Scholar
  • 23 Zeisberg M, Yang C, Martino M. et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 2007; 282 (32) 23337-23347
    CrossrefPubMedGoogle Scholar
  • 24 Robertson H, Kirby JA, Yip WW, Jones DE, Burt AD. Biliary epithelial-mesenchymal transition in posttransplantation recurrence of primary biliary cirrhosis. Hepatology 2007; 45 (04) 977-981
    CrossrefPubMedGoogle Scholar
  • 25 Omenetti A, Porrello A, Jung Y. et al. Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans. J Clin Invest 2008; 118 (10) 3331-3342
    PubMedGoogle Scholar
  • 26 Kagan HM. Intra- and extracellular enzymes of collagen biosynthesis as biological and chemical targets in the control of fibrosis. Acta Trop 2000; 77 (01) 147-152
    CrossrefPubMedGoogle Scholar
  • 27 Liu SB, Ikenaga N, Peng ZW. et al. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice. FASEB J 2016; 30 (04) 1599-1609
    CrossrefPubMedGoogle Scholar
  • 28 Tatsukawa H, Furutani Y, Hitomi K, Kojima S. Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death. Cell Death Dis 2016; 7 (06) e2244
    CrossrefPubMedGoogle Scholar
  • 29 Poynard T, McHutchison J, Manns M. et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002; 122 (05) 1303-1313
    CrossrefPubMedGoogle Scholar
  • 30 Issa R, Zhou X, Constandinou CM. et al. Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology 2004; 126 (07) 1795-1808
    CrossrefPubMedGoogle Scholar
  • 31 Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: direct antifibrotic agents and targeted therapies. Matrix Biol 2018; 68-69: 435-451
    CrossrefPubMedGoogle Scholar
  • 32 Huijberts MS, Schaper NC, Schalkwijk CG. Advanced glycation end products and diabetic foot disease. Diabetes Metab Res Rev 2008; 24 (Suppl. 01) S19-S24
    CrossrefPubMedGoogle Scholar
  • 33 Duarte S, Baber J, Fujii T, Coito AJ. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol 2015; 44-46: 147-156
    CrossrefPubMedGoogle Scholar
  • 34 Edwards DR, Handsley MM, Pennington CJ. The ADAM metalloproteinases. Mol Aspects Med 2008; 29 (05) 258-289
    CrossrefPubMedGoogle Scholar
  • 35 Dubail J, Apte SS. Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics. Matrix Biol 2015; 44-46: 24-37
    CrossrefPubMedGoogle Scholar
  • 36 Brix K, McInnes J, Al-Hashimi A, Rehders M, Tamhane T, Haugen MH. Proteolysis mediated by cysteine cathepsins and legumain-recent advances and cell biological challenges. Protoplasma 2015; 252 (03) 755-774
    CrossrefPubMedGoogle Scholar
  • 37 Beier JI, Arteel GE. Alcoholic liver disease and the potential role of plasminogen activator inhibitor-1 and fibrin metabolism. Exp Biol Med (Maywood) 2012; 237 (01) 1-9
    CrossrefPubMedGoogle Scholar
  • 38 Kisseleva T, Brenner DA. Hepatic stellate cells and the reversal of fibrosis. J Gastroenterol Hepatol 2006; 21 (Suppl. 03) S84-S87
    PubMedGoogle Scholar
  • 39 Pellicoro A, Aucott RL, Ramachandran P. et al. Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis. Hepatology 2012; 55 (06) 1965-1975
    CrossrefPubMedGoogle Scholar
  • 40 Natarajan V, Berglund EJ, Chen DX, Kidambi S. Substrate stiffness regulates primary hepatocyte functions. RSC Adv 2015; 5 (99) 80956-80966
    CrossrefPubMedGoogle Scholar
  • 41 Croce S, Peloso A, Zoro T, Avanzini MA, Cobianchi L. A hepatic scaffold from decellularized liver tissue: food for thought. Biomolecules 2019; 9 (12) 9
    CrossrefPubMedGoogle Scholar
  • 42 Modo M, Badylak SF. A roadmap for promoting endogenous in situ tissue restoration using inductive bioscaffolds after acute brain injury. Brain Res Bull 2019; 150: 136-149
    CrossrefPubMedGoogle Scholar
  • 43 Hussey GS, Cramer MC, Badylak SF. Extracellular matrix bioscaffolds for building gastrointestinal tissue. Cell Mol Gastroenterol Hepatol 2017; 5 (01) 1-13
    CrossrefPubMedGoogle Scholar
  • 44 Hodivala-Dilke KM, Reynolds AR, Reynolds LE. Integrins in angiogenesis: multitalented molecules in a balancing act. Cell Tissue Res 2003; 314 (01) 131-144
    CrossrefPubMedGoogle Scholar
  • 45 Zhou HF, Chan HW, Wickline SA, Lanza GM, Pham CT. Alphavbeta3-targeted nanotherapy suppresses inflammatory arthritis in mice. FASEB J 2009; 23 (09) 2978-2985
    CrossrefPubMedGoogle Scholar
  • 46 Humphries JD, Byron A, Humphries MJ. Integrin ligands at a glance. J Cell Sci 2006; 119 (Pt 19): 3901-3903
    CrossrefPubMedGoogle Scholar
  • 47 Patsenker E, Stickel F. Role of integrins in fibrosing liver diseases. Am J Physiol Gastrointest Liver Physiol 2011; 301 (03) G425-G434
    CrossrefPubMedGoogle Scholar
  • 48 Seth D, Duly A, Kuo PC, McCaughan GW, Haber PS. Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation. World J Gastroenterol 2014; 20 (36) 13088-13104
    CrossrefPubMedGoogle Scholar
  • 49 Patouraux S, Rousseau D, Bonnafous S. et al. CD44 is a key player in non-alcoholic steatohepatitis. J Hepatol 2017; 67 (02) 328-338
    CrossrefPubMedGoogle Scholar
  • 50 McDonald B, Kubes P. Interactions between CD44 and hyaluronan in leukocyte trafficking. Front Immunol 2015; 6: 68
    CrossrefPubMedGoogle Scholar
  • 51 Crosby HA, Lalor PF, Ross E, Newsome PN, Adams DH. Adhesion of human haematopoietic (CD34+) stem cells to human liver compartments is integrin and CD44 dependent and modulated by CXCR3 and CXCR4. J Hepatol 2009; 51 (04) 734-749
    CrossrefPubMedGoogle Scholar
  • 52 Gong H, Xu HM, Zhang DK. Focusing on discoidin domain receptors in premalignant and malignant liver diseases. Front Oncol 2023; 13: 1123638
    CrossrefPubMedGoogle Scholar
  • 53 Hansen NU, Genovese F, Leeming DJ, Karsdal MA. The importance of extracellular matrix for cell function and in vivo likeness. Exp Mol Pathol 2015; 98 (02) 286-294
    CrossrefPubMedGoogle Scholar
  • 54 Dolin CE, Arteel GE. The matrisome, inflammation, and liver disease. Semin Liver Dis 2020; 40 (02) 180-188
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2000; 1 (01) 31-39
    CrossrefPubMedGoogle Scholar
  • 56 Sadeghi S, Vink RL. Membrane sorting via the extracellular matrix. Biochim Biophys Acta 2015; 1848 (02) 527-531
    CrossrefPubMedGoogle Scholar
  • 57 Gay NJ, Gangloff M. Structure and function of toll receptors and their ligands. Annu Rev Biochem 2007; 76: 141-165
    CrossrefPubMedGoogle Scholar
  • 58 Ivaska J, Heino J. Cooperation between integrins and growth factor receptors in signaling and endocytosis. Annu Rev Cell Dev Biol 2011; 27: 291-320
    CrossrefPubMedGoogle Scholar
  • 59 Schnittert J, Bansal R, Storm G, Prakash J. Integrins in wound healing, fibrosis and tumor stroma: High potential targets for therapeutics and drug delivery. Adv Drug Deliv Rev 2018; 129: 37-53
    CrossrefPubMedGoogle Scholar
  • 60 Ozaki I, Hamajima H, Matsuhashi S, Mizuta T. Regulation of TGF-β1-induced pro-apoptotic signaling by growth factor receptors and extracellular matrix receptor integrins in the liver. Front Physiol 2011; 2: 78
    CrossrefPubMedGoogle Scholar
  • 61 Klaas M, Kangur T, Viil J. et al. The alterations in the extracellular matrix composition guide the repair of damaged liver tissue. Sci Rep 2016; 6: 27398
    CrossrefPubMedGoogle Scholar
  • 62 Coco B, Oliveri F, Maina AM. et al. Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat 2007; 14 (05) 360-369
    CrossrefPubMedGoogle Scholar
  • 63 Grgurevic I, Bozin T, Madir A. Hepatitis C is now curable, but what happens with cirrhosis and portal hypertension afterwards?. Clin Exp Hepatol 2017; 3 (04) 181-186
    CrossrefPubMedGoogle Scholar
  • 64 Ringer P, Colo G, Fässler R, Grashoff C. Sensing the mechano-chemical properties of the extracellular matrix. Matrix Biol 2017; 64: 6-16
    CrossrefPubMedGoogle Scholar
  • 65 Ge H, Tian M, Pei Q, Tan F, Pei H. Extracellular matrix stiffness: new areas affecting cell metabolism. Front Oncol 2021; 11: 631991
    CrossrefPubMedGoogle Scholar
  • 66 Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol 2010; 10 (10) 712-723
    CrossrefPubMedGoogle Scholar
  • 67 Lipowsky HH. Role of the glycocalyx as a barrier to leukocyte-endothelium adhesion. Adv Exp Med Biol 2018; 1097: 51-68
    CrossrefPubMedGoogle Scholar
  • 68 Karsdal MA, Manon-Jensen T, Genovese F. et al. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2015; 308 (10) G807-G830
    CrossrefPubMedGoogle Scholar
  • 69 Vempati P, Popel AS, Mac Gabhann F. Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning. Cytokine Growth Factor Rev 2014; 25 (01) 1-19
    CrossrefPubMedGoogle Scholar
  • 70 Werb Z. ECM and cell surface proteolysis: regulating cellular ecology. Cell 1997; 91 (04) 439-442
    CrossrefPubMedGoogle Scholar
  • 71 Wells JM, Gaggar A, Blalock JE. MMP generated matrikines. Matrix Biol 2015; 44-46: 122-129
    CrossrefPubMedGoogle Scholar
  • 72 Song KS, Kim HS, Park KE, Kwon OH. The fibrinogen degradation products (FgDP) levels in liver disease. Yonsei Med J 1993; 34 (03) 234-238
    CrossrefPubMedGoogle Scholar
  • 73 Santambrogio L, Rammensee HG. Contribution of the plasma and lymph degradome and peptidome to the MHC ligandome. Immunogenetics 2019; 71 (03) 203-216
    CrossrefPubMedGoogle Scholar
  • 74 Monneau Y, Arenzana-Seisdedos F, Lortat-Jacob H. The sweet spot: how GAGs help chemokines guide migrating cells. J Leukoc Biol 2016; 99 (06) 935-953
    CrossrefPubMedGoogle Scholar
  • 75 Ramaiah SK, Rittling S. Pathophysiological role of osteopontin in hepatic inflammation, toxicity, and cancer. Toxicol Sci 2008; 103 (01) 4-13
    CrossrefPubMedGoogle Scholar
  • 76 Godfrey HP. T cell fibronectin: an unexpected inflammatory lymphokine. Lymphokine Res 1990; 9 (03) 435-447
    PubMedGoogle Scholar
  • 77 D'Ardes D, Boccatonda A, Cocco G. et al. Impaired coagulation, liver dysfunction and COVID-19: discovering an intriguing relationship. World J Gastroenterol 2022; 28 (11) 1102-1112
    CrossrefPubMedGoogle Scholar
  • 78 Kangro K, Wolberg AS, Flick MJ. Fibrinogen, fibrin, and fibrin degradation products in COVID-19. Curr Drug Targets 2022; 23 (17) 1593-1602
    CrossrefPubMedGoogle Scholar
  • 79 Jennewein C, Tran N, Paulus P, Ellinghaus P, Eble JA, Zacharowski K. Novel aspects of fibrin(ogen) fragments during inflammation. Mol Med 2011; 17 (5-6): 568-573
    CrossrefPubMedGoogle Scholar
  • 80 Chiarugi P. From anchorage dependent proliferation to survival: lessons from redox signalling. IUBMB Life 2008; 60 (05) 301-307
    CrossrefPubMedGoogle Scholar
  • 81 Gough A, Soto-Gutierrez A, Vernetti L, Ebrahimkhani MR, Stern AM, Taylor DL. Human biomimetic liver microphysiology systems in drug development and precision medicine. Nat Rev Gastroenterol Hepatol 2021; 18 (04) 252-268
    CrossrefPubMedGoogle Scholar
  • 82 Manikat R, Ahmed A, Kim D. Current epidemiology of chronic liver disease. Gastroenterol Rep (Oxf) 2024; 12: goae069
    CrossrefPubMedGoogle Scholar
  • 83 Altamirano J, Bataller R. Alcoholic liver disease: pathogenesis and new targets for therapy. Nat Rev Gastroenterol Hepatol 2011; 8 (09) 491-501
    CrossrefPubMedGoogle Scholar
  • 84 Schwartz JM, Reinus JF. Prevalence and natural history of alcoholic liver disease. Clin Liver Dis 2012; 16 (04) 659-666
    CrossrefPubMedGoogle Scholar
  • 85 Bilson J, Scorletti E. Lipid droplets in steatotic liver disease. Curr Opin Clin Nutr Metab Care 2024; 27 (02) 91-97
    CrossrefPubMedGoogle Scholar
  • 86 Hammoutene A, Rautou PE. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J Hepatol 2019; 70 (06) 1278-1291
    CrossrefPubMedGoogle Scholar
  • 87 Qian S, Wang X, Chen Y, Zai Q, He Y. Inflammation in steatotic liver diseases: pathogenesis and therapeutic targets. Semin Liver Dis 2024; DOI: 10.1055/a-2338-9261.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 88 Kim HY, Sakane S, Eguileor A. et al. The origin and fate of liver myofibroblasts. Cell Mol Gastroenterol Hepatol 2024; 17 (01) 93-106
    CrossrefPubMedGoogle Scholar
  • 89 Osna NA, Eguchi A, Feldstein AE. et al. Cell-to-cell communications in alcohol-associated liver disease. Front Physiol 2022; 13: 831004
    CrossrefPubMedGoogle Scholar
  • 90 Wang R, Tang R, Li B, Ma X, Schnabl B, Tilg H. Gut microbiome, liver immunology, and liver diseases. Cell Mol Immunol 2021; 18 (01) 4-17
    CrossrefPubMedGoogle Scholar
  • 91 Baker NA, Muir LA, Washabaugh AR. et al. Diabetes-specific regulation of adipocyte metabolism by the adipose tissue extracellular matrix. J Clin Endocrinol Metab 2017; 102 (03) 1032-1043
    PubMedGoogle Scholar
  • 92 Roberts DD, Isenberg JS. CD47 and thrombospondin-1 regulation of mitochondria, metabolism, and diabetes. Am J Physiol Cell Physiol 2021; 321 (02) C201-C213
    CrossrefPubMedGoogle Scholar
  • 93 Song Z, Chen W, Athavale D. et al. Osteopontin takes center stage in chronic liver disease. Hepatology 2021; 73 (04) 1594-1608
    CrossrefPubMedGoogle Scholar
  • 94 Jia Y, Zhong F, Jiang S. et al. Periostin in chronic liver diseases: current research and future perspectives. Life Sci 2019; 226: 91-97
    CrossrefPubMedGoogle Scholar
  • 95 Lisman T, Jenne CN. Fibrin fuels fatty liver disease. J Thromb Haemost 2018; 16 (01) 3-5
    CrossrefPubMedGoogle Scholar
  • 96 Bays JL, Campbell HK, Heidema C, Sebbagh M, DeMali KA. Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK. Nat Cell Biol 2017; 19 (06) 724-731
    CrossrefPubMedGoogle Scholar
  • 97 Zhao X, Xue X, Wang C, Wang J, Peng C, Li Y. Emerging roles of sirtuins in alleviating alcoholic liver disease: a comprehensive review. Int Immunopharmacol 2022; 108: 108712
    CrossrefPubMedGoogle Scholar
  • 98 Romani P, Brian I, Santinon G. et al. Extracellular matrix mechanical cues regulate lipid metabolism through Lipin-1 and SREBP. Nat Cell Biol 2019; 21 (03) 338-347
    CrossrefPubMedGoogle Scholar
  • 99 Kroy DC, Schumacher F, Ramadori P. et al. Hepatocyte specific deletion of c-Met leads to the development of severe non-alcoholic steatohepatitis in mice. J Hepatol 2014; 61 (04) 883-890
    CrossrefPubMedGoogle Scholar
  • 100 Keles U, Ow JR, Kuentzel KB, Zhao LN, Kaldis P. Liver-derived metabolites as signaling molecules in fatty liver disease. Cell Mol Life Sci 2022; 80 (01) 4
    CrossrefPubMedGoogle Scholar
  • 101 Liang JQ, Liu C, Zhang WX, Chen SY. Interaction between hepatokines and metabolic diseases. Yi Chuan 2022; 44 (10) 853-866
    PubMedGoogle Scholar
  • 102 Colell A, García-Ruiz C, Miranda M. et al. Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 1998; 115 (06) 1541-1551
    CrossrefPubMedGoogle Scholar
  • 103 Pastorino JG, Hoek JB. Ethanol potentiates tumor necrosis factor-alpha cytotoxicity in hepatoma cells and primary rat hepatocytes by promoting induction of the mitochondrial permeability transition. Hepatology 2000; 31 (05) 1141-1152
    CrossrefPubMedGoogle Scholar
  • 104 Tsukamoto H, Lu SC. Current concepts in the pathogenesis of alcoholic liver injury. FASEB J 2001; 15 (08) 1335-1349
    CrossrefPubMedGoogle Scholar
  • 105 Shojaie L, Iorga A, Dara L. Cell death in liver diseases: a review. Int J Mol Sci 2020; 21 (24) 21
    CrossrefPubMedGoogle Scholar
  • 106 Miyata T, Nagy LE. Programmed cell death in alcohol-associated liver disease. Clin Mol Hepatol 2020; 26 (04) 618-625
    CrossrefPubMedGoogle Scholar
  • 107 Rozario T, DeSimone DW. The extracellular matrix in development and morphogenesis: a dynamic view. Dev Biol 2010; 341 (01) 126-140
    CrossrefPubMedGoogle Scholar
  • 108 Marastoni S, Ligresti G, Lorenzon E, Colombatti A, Mongiat M. Extracellular matrix: a matter of life and death. Connect Tissue Res 2008; 49 (03) 203-206
    CrossrefPubMedGoogle Scholar
  • 109 Nevi L, Safarikia S, Di Matteo S, Biancaniello F, Chiappetta MF, Cardinale V. Hyaluronan-based grafting strategies for liver stem cell therapy and tracking methods. Stem Cells Int 2019; 2019: 3620546
    CrossrefPubMedGoogle Scholar
  • 110 Mazza G, Al-Akkad W, Rombouts K, Pinzani M. Liver tissue engineering: from implantable tissue to whole organ engineering. Hepatol Commun 2017; 2 (02) 131-141
    CrossrefPubMedGoogle Scholar
  • 111 Mak KM, Mei R. Basement membrane type IV collagen and laminin: an overview of their biology and value as fibrosis biomarkers of liver disease. Anat Rec (Hoboken) 2017; 300 (08) 1371-1390
    CrossrefPubMedGoogle Scholar
  • 112 Li J, Sato T, Hernández-Tejero M. et al. The plasma degradome reflects later development of NASH fibrosis after liver transplant. Sci Rep 2023; 13 (01) 9965
    CrossrefPubMedGoogle Scholar
  • 113 Jariwala N, Ozols M, Bell M. et al. Matrikines as mediators of tissue remodelling. Adv Drug Deliv Rev 2022; 185: 114240
    CrossrefPubMedGoogle Scholar
  • 114 Seki E, Brenner DA. Recent advancement of molecular mechanisms of liver fibrosis. J Hepatobiliary Pancreat Sci 2015; 22 (07) 512-518
    CrossrefPubMedGoogle Scholar
  • 115 Louvet A, Mathurin P. Alcoholic liver disease: mechanisms of injury and targeted treatment. Nat Rev Gastroenterol Hepatol 2015; 12 (04) 231-242
    CrossrefPubMedGoogle Scholar
  • 116 Nejak-Bowen K, Orr A, Bowen Jr WC, Michalopoulos GK. Conditional genetic elimination of hepatocyte growth factor in mice compromises liver regeneration after partial hepatectomy. PLoS One 2013; 8 (03) e59836
    CrossrefPubMedGoogle Scholar
  • 117 Christophi C, Harun N, Fifis T. Liver regeneration and tumor stimulation – a review of cytokine and angiogenic factors. J Gastrointest Surg 2008; 12 (05) 966-980
    CrossrefPubMedGoogle Scholar
  • 118 Kim TH, Mars WM, Stolz DB, Petersen BE, Michalopoulos GK. Extracellular matrix remodeling at the early stages of liver regeneration in the rat. Hepatology 1997; 26 (04) 896-904
    CrossrefPubMedGoogle Scholar
  • 119 Digtyar AV, Pozdnyakova NV, Feldman NB, Lutsenko SV, Severin SE. Endostatin: current concepts about its biological role and mechanisms of action. Biochemistry (Mosc) 2007; 72 (03) 235-246
    CrossrefPubMedGoogle Scholar
  • 120 Kim IH, Kisseleva T, Brenner DA. Aging and liver disease. Curr Opin Gastroenterol 2015; 31 (03) 184-191
    CrossrefPubMedGoogle Scholar
  • 121 Fujita M, Sasada M, Iyoda T, Fukai F. Involvement of matricellular proteins in cellular senescence: potential therapeutic targets for age-related diseases. Int J Mol Sci 2024; 25 (12) 25
    CrossrefPubMedGoogle Scholar
  • 122 Mak KM, Chen LL, Lee TF. Codistribution of collagen type IV and laminin in liver fibrosis of elderly cadavers: immunohistochemical marker of perisinusoidal basement membrane formation. Anat Rec (Hoboken) 2013; 296 (06) 953-964
    CrossrefPubMedGoogle Scholar
  • 123 Rohn F, Kordes C, Buschmann T. et al. Impaired integrin α5 /β1-mediated hepatocyte growth factor release by stellate cells of the aged liver. Aging Cell 2020; 19 (04) e13131
    CrossrefPubMedGoogle Scholar
  • 124 Hensley MK, Deng JC. Acute on chronic liver failure and immune dysfunction: a mimic of sepsis. Semin Respir Crit Care Med 2018; 39 (05) 588-597
    Article in Thieme ConnectPubMedGoogle Scholar
  • 125 Li B, Selmi C, Tang R, Gershwin ME, Ma X. The microbiome and autoimmunity: a paradigm from the gut-liver axis. Cell Mol Immunol 2018; 15 (06) 595-609
    CrossrefPubMedGoogle Scholar
  • 126 Wree A, Marra F. The inflammasome in liver disease. J Hepatol 2016; 65 (05) 1055-1056
    CrossrefPubMedGoogle Scholar
  • 127 Gao B, Ahmad MF, Nagy LE, Tsukamoto H. Inflammatory pathways in alcoholic steatohepatitis. J Hepatol 2019; 70 (02) 249-259
    CrossrefPubMedGoogle Scholar
  • 128 Robinson MW, Harmon C, O'Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol 2016; 13 (03) 267-276
    CrossrefPubMedGoogle Scholar
  • 129 Beier JI, Luyendyk JP, Guo L, von Montfort C, Staunton DE, Arteel GE. Fibrin accumulation plays a critical role in the sensitization to lipopolysaccharide-induced liver injury caused by ethanol in mice. Hepatology 2009; 49 (05) 1545-1553
    CrossrefPubMedGoogle Scholar
  • 130 Gillis SE, Nagy LE. Deposition of cellular fibronectin increases before stellate cell activation in rat liver during ethanol feeding. Alcohol Clin Exp Res 1997; 21 (05) 857-861
    CrossrefPubMedGoogle Scholar
  • 131 Thiele GM, Duryee MJ, Freeman TL. et al. Rat sinusoidal liver endothelial cells (SECs) produce pro-fibrotic factors in response to adducts formed from the metabolites of ethanol. Biochem Pharmacol 2005; 70 (11) 1593-1600
    CrossrefPubMedGoogle Scholar
  • 132 Poole LG, Dolin CE, Arteel GE. Organ-organ crosstalk and alcoholic liver disease. Biomolecules 2017; 7 (03) 7
    CrossrefPubMedGoogle Scholar
  • 133 Massey VL, Dolin CE, Poole LG. et al. The hepatic “matrisome” responds dynamically to injury: characterization of transitional changes to the extracellular matrix in mice. Hepatology 2017; 65 (03) 969-982
    CrossrefPubMedGoogle Scholar
  • 134 Poole LG, Arteel GE. Transitional remodeling of the hepatic extracellular matrix in alcohol-induced liver injury. BioMed Res Int 2016; 2016: 3162670
    CrossrefPubMedGoogle Scholar
  • 135 Lorenz L, Axnick J, Buschmann T. et al. Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival. Nature 2018; 562 (7725) 128-132
    CrossrefPubMedGoogle Scholar
  • 136 Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 2007; 7 (09) 678-689
    CrossrefPubMedGoogle Scholar
  • 137 Shimizu Y, Shaw S. Lymphocyte interactions with extracellular matrix. FASEB J 1991; 5 (09) 2292-2299
    CrossrefPubMedGoogle Scholar
  • 138 Woodfin A, Voisin MB, Nourshargh S. Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol 2010; 17 (01) 9-17
    CrossrefPubMedGoogle Scholar
  • 139 Mak KM, Png CY, Lee DJ, Type V. Type V collagen in health, disease, and fibrosis. Anat Rec (Hoboken) 2016; 299 (05) 613-629
    CrossrefPubMedGoogle Scholar
  • 140 Schuster S, Cabrera D, Arrese M, Feldstein AE. Triggering and resolution of inflammation in NASH. Nat Rev Gastroenterol Hepatol 2018; 15 (06) 349-364
    CrossrefPubMedGoogle Scholar
  • 141 Widgerow AD. Cellular resolution of inflammation–catabasis. Wound Repair Regen 2012; 20 (01) 2-7
    CrossrefPubMedGoogle Scholar
  • 142 Franitza S, Hershkoviz R, Kam N. et al. TNF-alpha associated with extracellular matrix fibronectin provides a stop signal for chemotactically migrating T cells. J Immunol 2000; 165 (05) 2738-2747
    CrossrefPubMedGoogle Scholar
  • 143 Cañedo-Dorantes L, Cañedo-Ayala M. Skin acute wound healing: a comprehensive review. Int J Inflamm 2019; 2019: 3706315
    PubMedGoogle Scholar
  • 144 Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol 2021; 18 (03) 151-166
    CrossrefPubMedGoogle Scholar
  • 145 Schuppan D, Surabattula R, Wang XY. Determinants of fibrosis progression and regression in NASH. J Hepatol 2018; 68 (02) 238-250
    CrossrefPubMedGoogle Scholar
  • 146 Villesen IF, Daniels SJ, Leeming DJ, Karsdal MA, Nielsen MJ. Review article: the signalling and functional role of the extracellular matrix in the development of liver fibrosis. Aliment Pharmacol Ther 2020; 52 (01) 85-97
    CrossrefPubMedGoogle Scholar
  • 147 Villanueva A. Hepatocellular carcinoma. N Engl J Med 2019; 380 (15) 1450-1462
    CrossrefPubMedGoogle Scholar
  • 148 Jemal A, Ward EM, Johnson CJ. et al. Annual report to the nation on the status of cancer, 1975-2014, featuring survival. J Natl Cancer Inst 2017; 109 (09) 109
    CrossrefPubMedGoogle Scholar
  • 149 La Vecchia C, Negri E, Cavalieri d'Oro L, Franceschi S. Liver cirrhosis and the risk of primary liver cancer. Eur J Cancer Prev 1998; 7 (04) 315-320
    CrossrefPubMedGoogle Scholar
  • 150 Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004; 127 (5, Suppl 1): S35-S50
    CrossrefPubMedGoogle Scholar
  • 151 Rosmorduc O, Housset C. Hypoxia: a link between fibrogenesis, angiogenesis, and carcinogenesis in liver disease. Semin Liver Dis 2010; 30 (03) 258-270
    Article in Thieme ConnectPubMedGoogle Scholar
  • 152 Passi M, Zahler S. Mechano-signaling aspects of hepatocellular carcinoma. J Cancer 2021; 12 (21) 6411-6421
    CrossrefPubMedGoogle Scholar
  • 153 Kumada T, Toyoda H, Yasuda S. et al. Prediction of hepatocellular carcinoma by liver stiffness measurements using magnetic resonance elastography after eradicating hepatitis C virus. Clin Transl Gastroenterol 2021; 12 (04) e00337
    CrossrefPubMedGoogle Scholar
  • 154 Chen C, Wang Z, Ding Y, Qin Y. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol 2023; 14: 1133308
    CrossrefPubMedGoogle Scholar
  • 155 Ezhilarasan D, Najimi M. Deciphering the possible reciprocal loop between hepatic stellate cells and cancer cells in the tumor microenvironment of the liver. Crit Rev Oncol Hematol 2023; 182: 103902
    CrossrefPubMedGoogle Scholar
  • 156 Zhu C, Tabas I, Schwabe RF, Pajvani UB. Maladaptive regeneration - the reawakening of developmental pathways in NASH and fibrosis. Nat Rev Gastroenterol Hepatol 2021; 18 (02) 131-142
    CrossrefPubMedGoogle Scholar
  • 157 Wu Y, Qiao X, Qiao S, Yu L. Targeting integrins in hepatocellular carcinoma. Expert Opin Ther Targets 2011; 15 (04) 421-437
    CrossrefPubMedGoogle Scholar
  • 158 Sircana A, Paschetta E, Saba F, Molinaro F, Musso G. Recent insight into the role of fibrosis in nonalcoholic steatohepatitis-related hepatocellular carcinoma. Int J Mol Sci 2019; 20 (07) 20
    CrossrefPubMedGoogle Scholar
  • 159 Goodman SL, Picard M. Integrins as therapeutic targets. Trends Pharmacol Sci 2012; 33 (07) 405-412
    CrossrefPubMedGoogle Scholar
  • 160 Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889; 133: 571-573
    CrossrefPubMedGoogle Scholar
  • 161 Wu XZ, Chen D, Xie GR. Extracellular matrix remodeling in hepatocellular carcinoma: effects of soil on seed?. Med Hypotheses 2006; 66 (06) 1115-1120
    CrossrefPubMedGoogle Scholar
  • 162 Mielgo A, Schmid MC. Liver tropism in cancer: the hepatic metastatic niche. Cold Spring Harb Perspect Med 2020; 10 (03) 10
    CrossrefPubMedGoogle Scholar
  • 163 Obenauf AC, Massagué J. Surviving at a distance: organ-specific metastasis. Trends Cancer 2015; 1 (01) 76-91
    CrossrefPubMedGoogle Scholar
  • 164 Schulz PO, Ferreira FG, Nascimento MdeF. et al. Association of nonalcoholic fatty liver disease and liver cancer. World J Gastroenterol 2015; 21 (03) 913-918
    CrossrefPubMedGoogle Scholar
  • 165 Robinson SM, Wilson CH, Burt AD, Manas DM, White SA. Chemotherapy-associated liver injury in patients with colorectal liver metastases: a systematic review and meta-analysis. Ann Surg Oncol 2012; 19 (13) 4287-4299
    CrossrefPubMedGoogle Scholar
  • 166 Pathak S, Pandanaboyana S, Daniels I, Smart N, Prasad KR. Obesity and colorectal liver metastases: mechanisms and management. Surg Oncol 2016; 25 (03) 246-251
    CrossrefPubMedGoogle Scholar
  • 167 Naba A, Clauser KR, Whittaker CA, Carr SA, Tanabe KK, Hynes RO. Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC Cancer 2014; 14: 518
    CrossrefPubMedGoogle Scholar
  • 168 Hudson SV, Dolin CE, Poole LG. et al. Modeling the kinetics of integrin receptor binding to hepatic extracellular matrix proteins. Sci Rep 2017; 7 (01) 12444
    CrossrefPubMedGoogle Scholar
  • 169 Hudson SV, Miller HA, Mahlbacher GE. et al. Computational/experimental evaluation of liver metastasis post hepatic injury: interactions with macrophages and transitional ECM. Sci Rep 2019; 9 (01) 15077
    CrossrefPubMedGoogle Scholar
  • 170 Beattie AJ, Gilbert TW, Guyot JP, Yates AJ, Badylak SF. Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds. Tissue Eng Part A 2009; 15 (05) 1119-1125
    CrossrefPubMedGoogle Scholar
  • 171 Agrawal V, Johnson SA, Reing J. et al. Epimorphic regeneration approach to tissue replacement in adult mammals. Proc Natl Acad Sci U S A 2010; 107 (08) 3351-3355
    CrossrefPubMedGoogle Scholar
  • 172 Brown BN, Ratner BD, Goodman SB, Amar S, Badylak SF. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 2012; 33 (15) 3792-3802
    CrossrefPubMedGoogle Scholar
  • 173 Huleihel L, Bartolacci JG, Dziki JL. et al. Matrix-bound nanovesicles recapitulate extracellular matrix effects on macrophage phenotype. Tissue Eng Part A 2017; 23 (21-22): 1283-1294
    CrossrefPubMedGoogle Scholar
  • 174 Huleihel L, Hussey GS, Naranjo JD. et al. Matrix-bound nanovesicles within ECM bioscaffolds. Sci Adv 2016; 2 (06) e1600502
    CrossrefPubMedGoogle Scholar
  • 175 Mehal WZ, Schuppan D. Antifibrotic therapies in the liver. Semin Liver Dis 2015; 35 (02) 184-198
    Article in Thieme ConnectPubMedGoogle Scholar
  • 176 Pritchard MT, McCracken JM. Identifying novel targets for treatment of liver fibrosis: What can we learn from injured tissues which heal without a scar?. Curr Drug Targets 2015; 16 (12) 1332-1346
    CrossrefPubMedGoogle Scholar