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On-line Access: 2024-07-17

Received: 2023-05-09

Revision Accepted: 2023-07-29

Crosschecked: 2024-07-17

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Citations:  Bibtex RefMan EndNote GB/T7714


Yanjin WANG


Yifei CHEN


Yongmin YAN


Jianbo XI


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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.7 P.594-604


MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression

Author(s):  Yanjin WANG, Yifei CHEN, Fuji YANG, Xiaolong YU, Ying CHU, Jing ZHOU, Yongmin YAN, Jianbo XI

Affiliation(s):  Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Jiangsu University, Changzhou 213017, China; more

Corresponding email(s):   xjb@wjrmyy.cn, yym@wjrmyy.cn

Key Words:  Mesenchymal stem cell (MSC), Small extracellular vesicle (sEV), MicroRNA-4465 (miR-4465), Hepatic stellate cell (HSC), Liver fibrosis

Yanjin WANG, Yifei CHEN, Fuji YANG, Xiaolong YU, Ying CHU, Jing ZHOU, Yongmin YAN, Jianbo XI. MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression[J]. Journal of Zhejiang University Science B, 2024, 25(7): 594-604.

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author="Yanjin WANG, Yifei CHEN, Fuji YANG, Xiaolong YU, Ying CHU, Jing ZHOU, Yongmin YAN, Jianbo XI",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T MiR-4465-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 25
%N 7
%P 594-604
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300305

T1 - MiR-4465-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 - 25
IS - 7
SP - 594
EP - 604
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2300305

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 (HSCs) 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-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.


王岩金1,2, 陈逸菲2, 杨馥吉1,2, 虞晓龙3, 楚鹰3, 周静3, 严永敏1,3, 奚剑波3
1江苏大学附属武进医院检验科, 中国常州市, 213017
2江苏大学医学院检验医学系, 中国镇江市, 212013
3常州市分子诊断与肿瘤精准医学重点实验室, 徐州医科大学武进临床学院, 中国常州市, 213017


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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