Knockdown of circ_0044226 promotes endoplasmic reticulum stress-mediated autophagy and apoptosis in hepatic stellate cells via miR-4677-3p/SEC61G axis.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-06-01 Epub Date: 2024-02-29 DOI:10.1007/s10863-024-10007-0
Shanshan Yuan, Jiaming Liu, Li Yang, Xin Zhang, Kun Zhuang, Shuixiang He
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引用次数: 0

Abstract

Downregulation of circ_0044226 has been demonstrated to reduce pulmonary fibrosis, but the role of circ_0044226 in liver fibrosis remains to be explored. In this work, we found that circ_0044226 expression was upregulated during liver fibrosis. Knockdown of circ_0044226 inhibited proliferation, promoted autophagy and apoptosis of hepatic stellate cell LX-2. Bioinformatic analysis and dual luciferase reporter assays confirmed the interaction between circ_0044226, miR-4677-3p and SEC61G. Mechanistically, knockdown of circ_0044226 suppressed SEC61G expression by releasing miR-4677-3p, thereby enhancing endoplasmic reticulum stress. Overexpression of SEC61G or endoplasmic reticulum stress inhibitor 4-phenylbutiric acid partially reversed the effect of knockdown circ_0044226 on LX-2 cell function. In vivo experiments showed that inhibition of circ_0044226 attenuated CCL4-induced liver fibrosis in mice. These imply that circ_0044226 may be a potential target for the treatment of liver fibrosis.

Abstract Image

敲除circ_0044226可通过miR-4677-3p/SEC61G轴促进内质网应激介导的肝星状细胞自噬和凋亡。
已证实下调circ_0044226可减轻肺纤维化,但circ_0044226在肝纤维化中的作用仍有待探索。在这项研究中,我们发现circ_0044226在肝纤维化过程中表达上调。敲除circ_0044226可抑制肝星状细胞LX-2的增殖、促进自噬和凋亡。生物信息分析和双荧光素酶报告实验证实了circ_0044226、miR-4677-3p和SEC61G之间的相互作用。从机理上讲,circ_0044226的敲除通过释放miR-4677-3p抑制了SEC61G的表达,从而增强了内质网应激。过表达 SEC61G 或内质网应激抑制剂 4-苯基丁酸可部分逆转敲除 circ_0044226 对 LX-2 细胞功能的影响。体内实验表明,抑制 circ_0044226 可减轻 CCL4 诱导的小鼠肝纤维化。这意味着circ_0044226可能是治疗肝纤维化的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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