Semin Liver Dis 2001; 21(3): 351-372
DOI: 10.1055/s-2001-17556
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Matrix as a Modulator of Hepatic Fibrogenesis

Detlef Schuppan1 , Martin Ruehl2 , Rajan Somasundaram2 , Eckhart G. Hahn1
  • 1Department of Gastroenterology, Hepatology and Infectiology, University of Erlangen-Nuernberg, Erlangen, Germany
  • 2Klinikum Benjamin Franklin, Free University of Berlin, Berlin, Germany
Further Information

Publication History

Publication Date:
01 October 2001 (online)

ABSTRACT

The extracellular matrix (ECM) provides cells with positional information and a mechanical scaffold for adhesion and migration. It consists of collagens, glycoproteins, proteoglycans, glycosaminoglycans and molecules that are bound specifically by the ECM, such as certain growth factors/cytokines, matrix metalloproteinases (MMPs) and processing enzymes such as tissue transglutaminase and procollagen propeptidases. This finely tuned ecosystem is dysbalanced in chronic fibrogenesis, which can be regarded as a continuous wound-healing process and which results in scar formation. Importantly, the ECM directs cellular differentiation, migration, proliferation, and fibrogenic activation or deactivation. Partially via defined oligopeptide sequences or structural domains, the ECM transfers specific signals to cells that act in concert with growth factors/cytokines. These signals either confer stress activation, with a resultant fibrogenic response, or stress relaxation, with a fibrolytic response. Alternatively, ECM-derived peptides can modulate angiogenesis, or growth factor and MMP availability and activity. Current ECM-related antifibrotic strategies are based on the identification and in vivo application of ECM-derived biomodulatory peptides, peptide sequences, or their nonpeptidic mimetics. The latter open the opportunity of oral application and an extended biological half-life. Examples are peptides derived from collagens VI (stress activation) and XIV (stress relaxation), or collagenous consensus peptides that remove ECM-bound MMPs and growth factors. Furthermore, certain peptides can be used as targeting structures to the fibrogenic lesion.

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