过表达CXCL9的脐带间充质干细胞在体内外肝纤维化中的作用及机制

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Yang Li , Xueqian Zhang , Guiyu Liu , Tianci Tang , Xueshuai Ye , Jianhui Cai
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引用次数: 0

摘要

背景:脐带间充质干细胞(UC-MSCs)移植已成为一种有前景的肝纤维化治疗方法。然而,由于各种原因,UC-MSCs的抗纤维化能力有限。本研究旨在探讨CXCL9在uc - msc中的过表达(CXCL9- uc - msc)是否具有协同抗纤维化作用,并探讨其可能的机制。方法:建立大鼠肝纤维化模型,尾静脉注射CXCL9-UC-MSC细胞治疗。我们评估了不同治疗组对肝脏病变和肝功能的改善,同时进一步研究了TGF-β1/Smad3信号通路中各种蛋白的表达。此外,我们还监测了α-SMA、胶原蛋白iii和胶原蛋白i的表达水平。体外研究使用活化的LX-2细胞来验证细胞通路并评估活化的抑制作用。结果:细胞治疗后,病理染色及肝功能显示大鼠肝纤维化面积减小,肝细胞坏死减轻,肝功能损害改善。值得注意的是,这些改善在CXCL9-UC-MSC组中更为显著。此外,CXCL9干预后肝脏和LX-2细胞中α-SMA、胶原- iii、胶原- i、TGF-β1和pSmad3的表达水平均显著降低。此外,CXCL9的干预也显著抑制了LX-2细胞的增殖能力、生存能力和侵袭能力。结论:在UC-MSCs中过表达CXCL9抑制TGF-β1/Smad3信号通路的激活,降低肝脏和LX-2细胞中α-SMA、胶原- iii和胶原- i的表达,从而发挥更显著的抗纤维化作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The effect and mechanism of CXCL9 overexpressed umbilical cord mesenchymal stem cells on liver fibrosis in vivo and in vitro

Background

Umbilical cord mesenchymal stem cells (UC-MSCs) transplantation has emerged as a promising therapeutic approach of liver fibrosis. However, UC-MSCs have limited anti-fibrotic ability for various reasons. In this study, we aimed to investigate whether the overexpression of CXCL9 in UC-MSCs (CXCL9-UC-MSC) could have synergistic anti-fibrotic effects and explore the possible mechanism.

Methods

We established the rat models of liver fibrosis and administered CXCL9-UC-MSC cells via tail vein injection for therapy. We assessed the improvement in liver lesion and liver function across different treatment groups, while further investigating the expression of various proteins within the TGF-β1/Smad3 signaling pathway. Additionally, we monitored the expression levels of α-SMA, Collagen-III and Collagen-I. In vitro studies were conducted using activated LX-2 cells to validate the cellular pathways and assess inhibition of activation.

Results

After cell therapy, pathological staining and liver function indicated that the area of liver fibrosis in the rats was reduced, the hepatocellular necrosis was alleviated, and liver function damage was improved. Notably, these improvements were more significant in the CXCL9-UC-MSC group. Furthermore, the expression levels of α-SMA, Collagen-III, Collagen-I, TGF-β1 and pSmad3 in the liver and LX-2 cells were significantly decreased after the CXCL9 intervention. Additionally, the abilities of proliferation, viability and invasiveness of LX-2 cells were also significantly inhibited with the intervention of CXCL9.

Conclusion

The overexpression of CXCL9 in UC-MSCs inhibited the activation of the TGF-β1/Smad3 signaling pathway, and reduced the expressions of α-SMA, Collagen-III and Collagen-I in liver and LX-2 cells, thereby exerting a more significant anti-fibrotic effect.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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