Effect of Human Umbilical Cord Mesenchymal Stem Cells Transfected with HGF on TGF-β1/Smad Signaling Pathway in Carbon Tetrachloride-Induced Liver Fibrosis Rats

2020 ◽  
Vol 29 (21) ◽  
pp. 1395-1406
Author(s):  
Fei Yin ◽  
Wen-Ying Wang ◽  
Li-Cui Mao ◽  
Qi-Qi Cai ◽  
Wen-Hua Jiang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

scholarly journals Human Umbilical Cord Mesenchymal Stem Cells Ameliorate Hepatic Stellate Cell Activation and Liver Fibrosis by Upregulating MicroRNA-455-3p through Suppression of p21-Activated Kinase-2

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Qing Zhou ◽  
Tengfei Gu ◽  
Yong Zhang ◽  
Hongda Li ◽  
Xuemei Zhuansun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Umbilical Cord ◽  
Hepatic Stellate Cell ◽  
Target Gene ◽  
Stellate Cell ◽  
Luciferase Reporter ◽  
Human Umbilical Cord ◽  
P21 Activated Kinase

Mesenchymal stem cells (MSCs) were shown to have potential therapeutic effects for treatment of liver fibrosis, and dysregulated expression of microRNAs (miRNAs) played a pivotal role in the pathogenesis of liver fibrosis by regulating their downstream target genes. However, the mechanism by which MSCs affect the progression of liver fibrosis by regulating miRNA expression remains unclear. Here, we investigated whether human umbilical cord MSCs (HUC-MSCs) attenuated hepatic fibrosis by regulating miR-455-3p and its target gene. Significantly upregulated miRNA (miR-455-3p) was screened out by GEO datasets analysis and coculture HUC-MSCs with hepatic stellate cell (HSC) LX-2 cells. p21-activated kinase-2 (PAK2) was forecasted to be the target gene of miR-455-3p by bioinformatics analyses and confirmed by luciferase reporter assay. HUC-MSCs were transplanted into mice with carbon tetrachloride- (CCl4-) induced liver fibrosis, the result showed that HUC-MSC transplantation significantly ameliorated the severity of CCl4-induced liver fibrosis, attenuated collagen deposition, improved liver function by reducing the expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, upregulated miR-455-3p, and suppressed PAK2 expression of liver tissue in mice. Taken together, our study suggests that HUC-MSCs inhibit the activation of HSCs and mouse CCl4-induced liver fibrosis by upregulation of miR-455-3p through targeting PAK2.

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