Effect of ASIC1a on hepatic fibrosis under high glucose

WANG Huan1,2 WANG Ying-hong1,2 TIAN Yuan-yao1,2 SUN Shi-wei1,2 HUANG Meng-meng1,2 LI Xiao-feng1,2 MENG Xiao-ming1,2 HUANG Yan1,2

(1.Department of Basic & Clinical Pharmacology, School of Pharmacy, Anhui Medical University; Institute for Liver Diseases of Anhui Medical University, Hefei, China 230032)
(2.Institute for Liver Diseases of Anhui Medical University, Hefei ,China 230032)
【Knowledge Link】electrophoresis; mannitol; buffer; inhibitors

【Abstract】Aim To investigate the effect of ASIC1a (acid-sensing ion channel 1a) on the pathological change of diabetes complication liver fibrosis and the proliferation and activation of hepatic stellate cell (HSC-T6) stimulated by PDGF-BB under hyperglycemia. Methods Diabetes rats model was established by streptozotocin (STZ), and liver fibrosis rats model was induced by carbon tetrachloride (CCl4). Then, the extent of liver damage and the expression of ASIC1a were observed in the diabetic rats, liver fibrosis rats and diabetes complication liver fibrosis rats. In vitro, after pretreated with amiloride, HSC-T6 was treated with high glucose for 24 h and then stimulated with PDGF-BB for another 24 h. The proliferation and activation of HSC-T6 were observed, and the expression of ASIC1a, α-SMA and collagen Ⅰ were detected by Western blot. Results Compared with the control group, rats from diabetic group induced by STZ, liver fibrosis group induced by CCl4, and the diabetes complication liver fibrosis rats co-induced by STZ and CCl4 were all observed with liver damage at different levels, and tissue injury of complication group was the most serious. However, the expression of ASIC1a in the three model groups was significantly increased compared to the control group. ASIC1a level was the most obvious in the diabetes complication liver fibrosis rats. Amiloride pretreatment significantly decreased ASIC1a expression and inhibited PDGF-BB mediated proliferation and the expression of α-SMA and collagen Ⅰ in HSC-T6 under high glucose environment. Conclusion High ambient glucose aggravates HSC activation and hepatic fibrosis, and this may be related with the increasing expression of ASIC1a.

【Keywords】 high glucose; diabetes; hepatic stellate cell; acid-sensing ion channel 1a; hepatic fibrosis; activation and proliferation;

【DOI】

【Funds】 Anhui Province Academic and Technological Leaders Candidates Program (No. 2015H040) Key Projects of Anhui Provincial Universities Outstanding Young Talent Support Program (No. gxyq2016049) "Early Exposure to Research" Training Program of Anhui Medical University Clinical Medicine for ("5 + 3" integration) Special Students (No. 2015-ZQKY-46)

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This Article

ISSN:1001-1978

CN: 34-1086/R

Vol 32, No. 03, Pages 384-389

March 2016

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Abstract

  • 1 Materials and methods
  • 2 Results
  • 3 Discussion
  • References