Bone morphogenetic protein 7 suppresses the progression of hepatic fibrosis and regulates the expression of gremlin and transforming growth factor β1

Abstract

Bone morphogenetic protein 7 (BMP-7), a member of the transforming growth factor (TGF)-β superfamily, counteracts the effect of TGF-β through different signaling pathways, and gremlin is considered as one of the antagonists of BMP-7. The aim of this study was to investigate the antifibrotic effect of BMP-7, and to clarify the expression patterns of gremlin and TGF-β1 in the progression of hepatic fibrosis after treatment with BMP-7. A mouse liver fibrosis model was induced by hypodermic injection of CCL 4 and all the liver and blood samples were preserved for further study. Reverse transcription-polymerase chain reaction was used for detecting mRNA expression, and protein levels and localization were measured by western blotting and immunohistochemistry, respectively. The improvement of liver function and the regression of hepatic fibrosis were demonstrated by the parameters of a liver test and a histopathological assay, owing to the downregulated expression of COL-I, α-SMA, TIMP-2 and upregulated MMP-2. Moreover, exogenous BMP-7 appeared to suppress the expression of TGF-β1 and increase the levels of gremlin. In conclusion, hepatic fibrosis was ameliorated by the administration of BMP-7, and the expression of gremlin and TGF-β1 were regulated by BMP-7. The identification of the dynamic expression pattern of gremlin may yield a novel biomarker for assessing the degree of hepatic fibrosis.