Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases

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Herrera González, Blanca and Dooley, Steven and Breitkopf-Heinlein, Katja (2014) Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases. International Journal of Molecular Sciences, 15 (4). pp. 5199-5220. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms15045199




Abstract

Bone morphogenetic proteins (BMP-2 to BMP-15) belong to the Transforming Growth Factor (TGF)-β superfamily and, besides their well-documented roles during embryogenesis and bone formation, some of them have recently been described to be involved in the pathogenesis of different organs, including the liver. The role of BMPs in liver damage responses including hepatocellular carcinoma (HCC) development has only begun to be addressed and strong evidence supports the concept of a pro-tumorigenic role of BMP signaling in HCC cells. BMP-9 (also termed Growth and Differentiation Factor (GDF)-2) represents the most recently discovered member of the BMP family. We have previously demonstrated that in HCC patient samples BMP-9 expression was positively associated with the tumor seize (“T stage”) and that it enhanced cell migration and induced epithelial to mesenchymal transition (EMT) in HCC cells in vitro. In another study we recently found that BMP-9 promotes growth in HCC cells, but not in non-transformed hepatocytes. Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes the epithelial phenotype and inhibits proliferation, in HCC cells it induces cell growth and the acquisition of a migratory phenotype. In this review article we summarize current knowledge about BMPs in liver diseases, with special focus on the role of BMP-9 in HCC development and progression, that may provide new clues for a better understanding of the contribution of BMP-signaling to chronic liver diseases.


Item Type:Article
Uncontrolled Keywords:BMP-9; Hepatocellular carcinoma; signaling; physiology; liver; hepatocytes; hepatic stellate cells; angiogenesis; therapy
Subjects:Medical sciences > Medicine > Gastroenterology and Hepatology
Medical sciences > Medicine > Medical microbiology
Medical sciences > Pharmacy > Molecular biology
Medical sciences > Pharmacy > Biochemistry
ID Code:67114
Deposited On:22 Jul 2021 14:34
Last Modified:17 Aug 2021 08:29

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