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MiR4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression
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Yanjin WANG, Yifei CHEN, Fuji YANG, Xiaolong YU, Ying CHU, Jing ZHOU, Yongmin YAN, Jianbo XI. MiR4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .
@article{title="MiR4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression",
author="Yanjin WANG, Yifei CHEN, Fuji YANG, Xiaolong YU, Ying CHU, Jing ZHOU, Yongmin YAN, Jianbo XI",
journal="Journal of Zhejiang University Science B",
volume="-1",
number="-1",
pages="",
year="1998",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300305"
}
%0 Journal Article
%T MiR4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression
%A Yanjin WANG
%A Yifei CHEN
%A Fuji YANG
%A Xiaolong YU
%A Ying CHU
%A Jing ZHOU
%A Yongmin YAN
%A Jianbo XI
%J Journal of Zhejiang University SCIENCE B
%V -1
%N -1
%P
%@ 1673-1581
%D 1998
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300305
TY - JOUR
T1 - MiR4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression
A1 - Yanjin WANG
A1 - Yifei CHEN
A1 - Fuji YANG
A1 - Xiaolong YU
A1 - Ying CHU
A1 - Jing ZHOU
A1 - Yongmin YAN
A1 - Jianbo XI
J0 - Journal of Zhejiang University Science B
VL - -1
IS - -1
SP -
EP -
%@ 1673-1581
Y1 - 1998
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300305
Abstract: liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSC) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for miRNA delivery into target cells or tissues. It is currently unclear whether miR4465 can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR4465-modified MSC-sEV (MSC-sEVmiR4465) on LOXL2 expression and liver fibrosis development. The results showed that miR4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.
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