Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597365
1. Fibrogenesis
Georg Thieme Verlag KG Stuttgart · New York

Hypoxia causes hepatic stellate cells activation in the absence of CUX1

E Becker
1   Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Marburg, Germany
,
P Di Fazio
1   Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Marburg, Germany
,
J Hänze
2   Philipps University Marburg, Department of Urology, Marburg, Germany
,
DK Bartsch
1   Philipps University Marburg, Department of Visceral, Thoracic and Vascular Surgery, Marburg, Germany
,
T Gress
3   Philipps University Marburg, Department of Gastroenterology, Marburg, Germany
,
TT Wissniowski
3   Philipps University Marburg, Department of Gastroenterology, Marburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2016 (online)

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Background and Aim: CUX1 (CUTL1) is a transcription factor belonging to homeobox proteins. It is responsible of driving the transcription of genes deputed to many cellular functions like proliferation, differentiation and cell death.

It has been shown that its role can change and drive tumorigenesis. Up to now, its role is unknown in hepatic stellate cells. We focused on CUX1 activity in hepatic stellate cells undergoing hypoxic stress.

Methods: LX-2 cells were treated with 100 ng/ml CoCl2 or kept at 37 ° C at lox oxygen (< 0.5%). Expression of hypoxia markers and activation markers was performed by RT-qPCR. Western blotting was performed to analyze the protein level of CUX1 and HIF-1alpha.

Results: LX-2 cells treated for 6 hours with CoCl2 or low oxygen showed an over-expression or a restoration of COL1A1 and ACTA2 after knock down of CUX1. Additionally, CDKN1A, CDKN1B, VEGFA and HIF1alpha were up-regulated in LX.2 cells previously transfected with siCUX1. Protein level of CUX1 was significantly down-regulated, whereas HIF1alpha protein was strongly up-regulated by hypoxia condition.

Conclusion: CUX1 controls the activation of hepatic stellate cells. Its knock down promotes the hypoxia response. CUX1 could represent a key factor for controlling liver fibrogenesis. Its role in a liver fibrosis scenario needs to be further investigated.