GPR91 antagonist and TGF-β inhibitor suppressed collagen production of high glucose and succinate induced HSC activation
| Autor: | Takuma Aoyama, Ryoichi Yoshimura, Mutsuko Sakai, Kenji Urayama, Takaaki Sumiyoshi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male Biophysics Succinic Acid Biochemistry Receptors G-Protein-Coupled Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Liver stiffness Transforming Growth Factor beta Quinoxalines Gene expression Hepatic Stellate Cells Animals Receptor Molecular Biology Cells Cultured Chemistry Antagonist Imidazoles hemic and immune systems Cell Biology Cell biology 030104 developmental biology Glucose 030220 oncology & carcinogenesis High glucose Hepatic stellate cell Collagen Type I collagen Transforming growth factor |
| Zdroj: | Biochemical and biophysical research communications. 530(2) |
| ISSN: | 1090-2104 |
| Popis: | Activated hepatic stellate cells (HSCs) play a central role in fibrillary collagen production, the primary cause of liver fibrosis. Although it is known that primary cultured HSCs are activated by plastic culture dish stiffness, HSC activation and quiescent-state-reversion mechanisms are still unclear. In this study, we used cultured normal rat HSCs on 3.2 kPa collagen normal liver stiffness equivalent gel, to determine whether high glucose or high succinate conditions induce HSC activation, and examined whether activated HSCs reverted to a quiescent state when suppressed by GPR91 antagonists or TGF-β1 receptor inhibitors. We measured the gene expression levels of α-SMA and type I collagen HSC activation markers using real-time PCR. Our data indicated that high glucose conditions induced HSC activation, and showed that under continuous high glucose exposure HSC activation progressed. A GPR91 antagonist, 2 d, and a TGF-β1 receptor inhibitor, SB525334, suppressed the Col1α mRNA expression level of these activated HSCs. Similarly, under extended high succinate exposure, 2 d and SB525334 reduced Col1α mRNA expression levels of activated HSCs. From the above, we determined that even though HSCs had already been activated by high glucose or succinate conditions which persisted after activation, the GPR91 antagonist and the TGF-β1 receptor inhibitor were able to reduce the production of type I collagen from activated HSCs. |
| Databáze: | OpenAIRE |
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