HGF is known to inhibit accumulation of extracellular matrix and development of hepatic fibrosis in vivo. TGF-b can in turn dramatically suppress HGF mRNA expression in HSC, demonstrating the reciprocal effects of these cytokines on ECM accumulation. The synthesis of extracellular matrix proteins is modulated by microRNA-29 in extrahepatic tissue. Recent reports suggest that miR-29 is also involved in the synthesis of collagen type I in liver fibrosis. The miR-29 family consists of miR-29a, miR-29b, and miR-29c, which differ in only two or three nucleotides, respectively. The genes for miR-29a and miR-29b1 are both located on chromosome 7, whereas the genes for miR-29c and miR-29b2 are located on chromosome 1. Each gene pair is transcribed in tandem resulting in a common pri-miRNA from which the mature miR-29 members are released after further processing. In the present study, we investigate the role of the members of the miR-29 family in HGF mediated repression of collagen synthesis. We AbMole 4-Chloropropiophenone demonstrate that miR-29 is not only involved in collagen type I but also in type IV synthesis of myofibroblastic HSC. The importance of miR-29 in hepatic collagen homeostasis is underlined by our in vivo data that shows the lack of miR-29 in severe experimental fibrosis after bile duct obstruction. This loss of miR-29 is suggested to be due to the response of HSC to exposure to profibrogenic mediators as shown by our in vitro findings on TGF-b stimulated HSC. Whereas TGF-b stimulation leads to decreased miR-29 levels, but to pronounced upregulation of collagen synthesis, HGF stimulation leads to elevated miR-29 expression, but to repression of collagen synthesis. Thus, our data provide detailed evidence for the antifibrotic action of miR-29 in response to HGF signalling that is counteracted by the profibrotic growth factor TGF-b. In the present study we investigated the effects of the opposing action of TGF-b and HGF on miR-29 regulated collagen synthesis by HSC during liver fibrosis. After transdifferentiation into myofibroblasts, HSC constitute the main matrix producing cell type of the fibrotic liver. Our findings demonstrate that myofibroblastic transdifferentiation is accompanied by the loss of HGF synthesis on the one hand, and a tremendous increase of Met receptor expression on the other hand. Previous data have shown that the transition of HSC into myofibroblasts is triggered by paracrine but also by autocrine TGF-b stimulation. Accordingly, TGF-b treatment of HSC leads to decreased HGF expression, but enhanced Met receptor synthesis. Although Ikeda et al have suggested that Met receptor expression only AbMole Trihexyphenidyl HCl occurs in myofibroblastic HSC, its upregulation in response to TGF-b and its association with the pro-fibrotic effects of TGF-b has not been previously shown.