Background & aims: Matrilins are a family of four oligomeric adaptor proteins whose functions in extracellular matrix assembly during pathophysiological events still need to be explored in more detail. Matrilin-2 is the largest family member and the only matrilin expressed in the naive liver. Several studies demonstrate that matrilin-2 interacts with collagen I, fibronectin or laminin-111-nidogen-1 complexes. All these matrix components get upregulated during hepatic scar tissue formation. Therefore, we tested whether matrilin-2 has an influence on the formation and/or the resolution of fibrotic tissue in the mouse liver.
Methods: Fibrosis was induced by infection with an adenovirus encoding cytochrome P450 2D6 (autoimmune liver damage) or by exposure to the hepatotoxin carbon tetrachloride. Fibrosis severity and matrilin-2 expression were assessed by immunohistochemistry. Hepatic stellate cells (HSCs) were isolated and analysed by immunocytochemistry and Transwell migration assays.
Results: Both autoimmune as well as chemically induced liver damage led to simultaneous upregulation of matrilin-2 and collagen I expression. Discontinuation of carbon tetrachloride exposure resulted in concomitant dissolution of both proteins. Activated HSCs were the source of de novo matrilin-2 expression. Comparing wild type and matrilin-2-deficient mice, no differences were detected in fibronectin and collagen I upregulation and resolution kinetics as well as amount or location of fibronectin and collagen I production and degradation.
Conclusions: Our findings suggest that the absence of matrilin-2 has no effect on HSC activation and regression kinetics, synthetic activity, proliferative capacity, motility, or HSC apoptosis.
Keywords: adaptor molecule; extracellular matrix; fibrosis regression; hepatic stellate cell; liver fibrosis; matrilin-2.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.