文献类型：期刊文献

英文题名：Advanced glycation end product (AGE)-induced hepatic stellate cell activation via autophagy contributes to hepatitis C-related fibrosis

作者：He, YingLi Zhu, JinQiu Huang, YaQi Gao, Heng Zhao, YingRen

第一作者：He, YingLi

通信作者：Zhu, JQ[1]

机构：[1]Xi An Jiao Tong Univ, Sch Med, Affiliated Teaching Hosp 1, Dept Infect Dis, Xian 710049, Shaanxi Provinc, Peoples R China;[2]Guizhou Inst Technol, Sch Pharmaceut Engn, Guiyang 550003, Guizhou, Peoples R China;[3]Xian Hlth Sch, Xian, Shaanxi Provinc, Peoples R China;[4]Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Inst Hepatol, Xian 710049, Shaanxi Provinc, Peoples R China;[5]Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Infect Dis, Xian 710049, Shaanxi, Peoples R China

第一机构：Xi An Jiao Tong Univ, Sch Med, Affiliated Teaching Hosp 1, Dept Infect Dis, Xian 710049, Shaanxi Provinc, Peoples R China

通信机构：corresponding author), Guizhou Inst Technol, Sch Pharmaceut Engn, Guiyang 550003, Guizhou, Peoples R China.|贵州理工学院食品药品制造工程学院;贵州理工学院;

年份：2015

卷号：52

期号：5

起止页码：959-969

外文期刊名：ACTA DIABETOLOGICA

收录：;Scopus(收录号：2-s2.0-84941932908);WOS:【SCI-EXPANDED(收录号:WOS:000361346500017)】；

基金：This study was supported by grants from the China National Natural Science Foundation (No. 30700712), and the Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China) (No. 2008ZX10002-007, No. 2012ZX10002007) and the Fundamental Research Funds for the Central Universities. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

外文关键词：Autophagy; Fibrosis; Insulin resistance; Advanced glycation end products; Hepatitis C; Hepatic stellate cells

摘要：Aims Advanced glycation end products (AGEs) have been implicated in pulmonary and renal fibrosis. Herein, we investigated whether AGEs are associated with liver fibrosis and examined the underlying mechanism by focusing on hepatic stellate cell (HSC) activation and autophagy induction. Methods Liver fibrosis was assessed by transient elastography (FibroScan). Serum AGE levels were determined by ELISA. Rat primary HSCs and HSC-T6 were treated with BSA-AGEs, cell proliferation was examined by WST-1 assay, and cell activation was evaluated by qPCR for transcripts of alpha-SMA and collagen type I alpha 1 and by Western blotting. Autophagy was measured by detection of LC3-II lipidation, p62 degradation, and puncta GFP-LC3 formation. Receptor of AGE (RAGE)-blocking antibodies and soluble RAGE were employed to inhibit AGE-RAGE signaling. Results First, elevated AGE levels were observed in CHC patients than patients with chronic hepatitis B, especially in those with insulin resistance. Second, compared to controls, AGE-treated rat primary HSCs displayed an enhanced cell proliferation (1.39-fold), increased transcripts of alpha-SMA (2.40-fold) and proCOL1A1 (1.76-fold), and a higher level of alpha-SMA protein (1.85-fold). Moreover, AGE-induced HSC activation improved autophagy flux, as evidenced by significantly more LC3-II lipidation, p62 degradation, as well as GFP-LC3 puncta formations. In addition, our results showed that AGE-induced HSC autophagy and HSC activation could be reduced by RAGEs. Conclusion AGEs were found to induce autophagy and activation of HSCs, which subsequently contributes to the fibrosis in CHC patients. Blocking AGE-RAGE signaling may be a promising way to alleviate fibrosis.