骨髓间充质干细胞来源的外泌体通过miR-144-3p/SLC7A11轴抑制肝星状细胞的激活。
Bone marrow mesenchymal stem cell-originated exosomes suppress activation of hepatic stellate cells through the miR-144-3p/SLC7A11 axis.
作者信息
Hao Yanqin, Wang Rong, Zhou Qing, Ren Jiaolong
机构信息
Department of Infectious Diseases, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.
The First Clinical Medical School, Shanxi Medical University, Taiyuan, Shanxi, P.R. China.
出版信息
Clin Exp Hepatol. 2024 Sep;10(3):197-210. doi: 10.5114/ceh.2024.142898. Epub 2024 Sep 30.
AIM OF THE STUDY
This study aimed to investigate the impact of bone marrow-derived mesenchymal stem cell exosomes (BMSC-Exos) on hepatic stellate cell (HSC) activation and explore the underlying molecular mechanisms in liver fibrosis.
MATERIAL AND METHODS
BMSC-Exos were co-incubated with LPS-activated LX-2 cells. Fibrosis markers, iron content, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) levels, and ferroptosis-related proteins were assessed. The role of miR-144-3p originating from BMSC-Exos in LX-2 cell activation was studied through dual-luciferase reporter gene and RNA pull-down experiments.
RESULTS
Treatment with BMSC-Exos up-regulated miR-144-3p in LX-2 cells, down-regulated SLC7A11, increased iron content and ROS levels, and reduced fibrosis markers and GSH. BMSC-Exos mediated ferroptosis and inhibited HSC activation by transmitting miR-144-3p targeting SLC7A11.
CONCLUSIONS
BMSC-Exos regulate SLC7A11 expression through miR-144-3p transfer, promoting ferroptosis and suppressing HSC activation in liver fibrosis.
研究目的
本研究旨在探讨骨髓间充质干细胞外泌体（BMSC-Exos）对肝星状细胞（HSC）激活的影响，并探索肝纤维化潜在的分子机制。
材料与方法
将BMSC-Exos与脂多糖激活的LX-2细胞共同孵育。评估纤维化标志物、铁含量、丙二醛（MDA）、谷胱甘肽（GSH）、活性氧（ROS）水平以及铁死亡相关蛋白。通过双荧光素酶报告基因和RNA下拉实验研究源自BMSC-Exos的miR-144-3p在LX-2细胞激活中的作用。
结果
用BMSC-Exos处理上调了LX-2细胞中miR-144-3p的表达，下调了溶质载体家族7成员11（SLC7A11），增加了铁含量和ROS水平，并降低了纤维化标志物和GSH。BMSC-Exos通过传递靶向SLC7A11的miR-144-3p介导铁死亡并抑制HSC激活。
结论
BMSC-Exos通过miR-144-3p转移调节SLC7A11表达，促进铁死亡并抑制肝纤维化中的HSC激活。
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