Hepatic injuries due to viral infection and alcoholic abuse frequently lead to activation and proliferation of hepatic stellate cells (HSCs), concomitantly with tissue repairing and remodeling mechanism. Transforming growth factor-£]1 (TGF-£]1) is known to be one of the potent cytokines that directly upregulates synthesis of extracellular matrix, thereby aggravating liver fibrosis. Bone morphogenetic protein-2 (BMP-2), as a member of TGF-Hepatic injuries due to viral infection and alcoholic abuse frequently lead to activation and proliferation of hepatic stellate cells (HSCs), concomitantly with tissue repairing and remodeling mechanism. Transforming growth factor-£]1 (TGF-£]1) is known to be one of the potent cytokines that directly upregulates synthesis of extracellular matrix, thereby aggravating liver fibrosis. Bone morphogenetic protein-2 (BMP-2), as a member of TGF-£]1 superfamily, has been known to regulate cell proliferation, differentiation, and bone morphogenesis. Our previous study demonstrated that BMP-2 was downregulated in fibrotic liver of mice, supporting its antagonistic role in hepatic fibrogenesis. Downregulation of BMP-2 in fibrotic livers may lose its ability to antagonize the pro-fibrogenic action of TGF-£]1. The purpose of this study was to determine whether mutual regulatory mechanisms exist between BMP-2 and TGF-£]1.
Treatment of recombinant protein, TGF-£]1, significantly suppressed BMP-2 expression in hepatocytes clone-9 and HSC-T6 cells. Moreover, treatment of BMP-2 in both cell also attenuated TGF-£]1protein levels in a dose-dependent manner. This finding supports that TGF-£]1 and BMP-2 mutually modulated their expression not only in vivo, but also in vitro. Western blotting analysis showed that TGF-£]1 and BMP-2 exerted different kinase phosphorylation profiles of signaling activities. However, the signal pathways and detail mechanisms of the interactions of BMP-2 and TGF-£]1 in the fibrogenic action will need to further evaluate.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0824110-131729 |
| Date | 24 August 2010 |
| Creators | Wu, Yi-Chen |
| Contributors | hu-tsung Hui, Ching-mei Hsu, ming-hong Tai |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0824110-131729 |
| Rights | off_campus_withheld, Copyright information available at source archive |
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