HIV and HCV Co-Culture Promotes Profibrogenic Gene Expression through an Epimorphin-Mediated ERK Signaling Pathway in Hepatic Stellate Cells.
HIV and HCV Co-Culture Promotes Profibrogenic Gene Expression through an Epimorphin-Mediated ERK Signaling Pathway in Hepatic Stellate Cells.
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HIV 和 HCV 共培养通过肝星状细胞中 Epimorphin 介导的 ERK 信号通路促进促纤维化基因表达
DOI：
10.1371/journal.pone.0158386
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Shi L;Qin E;Zhou J;Zhao J;Nie W;Jiang T;Chen W;Wu D;Huang L;Liu L;Lv L;Zhao M;Zhang Z;Wang F
在高效抗逆转录病毒治疗（HAART）时代，丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）合并感染患者的加速纤维化已成为死亡的主要原因。然而，合并感染在加速肝纤维化进展中的作用，特别是合并感染对肝星状细胞（HSC）的影响仍不清楚。我们假设 HIV 和 HCV 通过改变 Epimorphin 产生的调节协同诱导肝纤维化，从而间接改变 HSC 功能。在这里，我们检查了 Epimorphin 对 HSC 增殖和侵袭的影响，以及在灭活 CXCR4 倾向的 HIV 和 HCV (JFH1) 存在下 HSC (LX2) 中纤维发生相关基因活性的变化。 HIV和HCV的结合显着增加了epimorphin的表达，从而增加了HSC的增殖和侵袭能力。 Epimorphin 还以细胞外信号调节激酶 (ERK) 依赖性方式诱导促纤维化组织金属蛋白酶 1 抑制剂 (TIMP1) 的表达。这些数据表明，HIV/HCV 混合感染对肝纤维化的影响可能部分是由 EPM 介导的。限制 EPM 表达的策略可能代表了一种预防 HIV/HCV 合并感染期间肝纤维化进展的新治疗方法。
Accelerated fibrosis in patients co-infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been a major cause of mortality in the highly active anti-retroviral therapy (HAART) era. However, the role of co-infection in accelerating the progression of liver fibrosis, particularly with regard to the effects of co-infection on hepatic stellate cells (HSCs), remains unclear. We hypothesized that HIV and HCV induce liver fibrosis synergistically by altering the regulation of epimorphin production, and thereby indirectly alter HSC function. Here, we examined the effects of epimorphin on HSC proliferation and invasion, and the changes in fibrogenesis-related gene activity in HSCs (LX2) in the presence of inactivated CXCR4-tropic HIV and HCV (JFH1). The combination of HIV and HCV significantly increased epimorphin expression, which increased the proliferation and invasion capabilities of HSCs. Epimorphin also induced the expression of profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP1) in an extracellular signal-regulated kinase (ERK)-dependent manner. These data indicated that the effects of HIV/HCV co-infection on hepatic fibrosis might be mediated in part by EPM. Strategies to limit the expression of EPM might represent a novel therapeutic approach to prevent the progression of hepatic fibrosis during HIV/HCV co-infection.