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

Abstract

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.

The Role of Butylidenephthalide in Targeting the Microenvironment Which Contributes to Liver Fibrosis Amelioration

“…These results connect correlate? with previous studies on liver and renal fibrosis ( Zeisberg et al, 2003 ; Kinoshita et al, 2007 ; Yang et al, 2012 ), suggesting that BMP-7 is one of the possible mechanisms in reversing liver fibrosis by counteracting TGF-β and EMT ( Zeisberg et al, 2003 ).…”

Lung Remodeling in a Mouse Model of Asthma Involves a Balance between TGF-β1 and BMP-7

“…There is data showing that on a model of hepatic fibrosis, the BMP-7 RNA levels in the liver are the same whether the animals are treated or not with BMP-7. Also, treatment with BMP-7 increases the levels of Gremlin, which is an antagonist that prevents BMP-7's ligation to its receptor [27]. Despite the different variables that can influence the effect of in vivo treatment with BMP-7, our work is the first description of the anti-fibrotic role of BMP-7 in an allergic setting, such as asthma.…”

Reduced expression of BMP3 contributes to the development of pulmonary fibrosis and predicts the unfavorable prognosis in IIP patients

“…Balanced TGF-β and BMP signaling has been proposed to be crucial for the progression of fibrosis [ 42 ]. Meng et al suggested that TGF-β1 is activated upon fibrosis, disrupting the balance between TGF-β1 and BMP7 resulted in the suppression of BMP7 expression and its target genes [ 33 , 43 ]. Similarly, in the present study, a mutually inhibitory relationship between TGF-β1 and BMP3 was observed in both human patients and a murine fibrosis model.…”

“…Immunohistochemical staining The lung biopsies of 83 patients were performed immunohistochemical staining to determine the expression of BMP3 and TGF-β. Among these patients, the biopsies of 47 cases were used to establish the tissue arrays following a method previously described (Shanghai Outdo Biotech Co. Ltd) [ 33 ], which were possess the integrated five-years following-up data. Briefly, tissue arrays were constructed from 154 tissue samples collected from 47 lung thoracoscopic surgery specimens of patients with IPF and INSIP (Each specimen was randomly taken 3 samples to construct tissue arrays), and 13 normal tissue specimens (Each specimen was randomly taken 1 sample for construction).…”