Yang Li , Xueqian Zhang , Guiyu Liu , Tianci Tang , Xueshuai Ye , Jianhui Cai
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引用次数: 0
Abstract
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.
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.