Human umbilical cord mesenchymal stem cell-derived exosomes alleviate pulmonary fibrosis in mice by inhibiting epithelial-mesenchymal transition.
10.12122/j.issn.1673-4254.2020.07.11
- Author:
Jing YANG
1
;
Huazhong HU
1
;
Shuqin ZHANG
1
;
Linrui JIANG
1
;
Yuanxiong CHENG
2
;
Haojun XIE
2
;
Xiaoyan WANG
3
;
Jiaohua JIANG
3
;
Hong WANG
4
;
Qun ZHANG
1
Author Information
1. Office of National Clinical Trials of Drugs, Guangzhou 510000, China.
2. Department of Respiratory and Critical Care Medicine, Guangzhou 510000, China.
3. Guangzhou Saliai Stem Cell Science and Technology Company Limited, Guangzhou 510080, China.
4. Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou 510000, China.
- Publication Type:Journal Article
- Keywords:
TGF-β1/Smad2/3;
epithelial-mesenchymal transition;
human umbilical cord mesenchymal stem cell derived exosomes;
idiopathic pulmonary fibrosis
- MeSH:
Animals;
Epithelial-Mesenchymal Transition;
Exosomes;
Humans;
Mesenchymal Stem Cells;
Mice;
Pulmonary Fibrosis;
Transforming Growth Factor beta1;
Umbilical Cord
- From:
Journal of Southern Medical University
2020;40(7):988-994
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the anti- fibrotic effect of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) and explore the mechanism.
METHODS:Twenty-four C57 BL/6 mice were divided into 4 groups (=6), including the control group treated with intratracheal injection of saline (3 mg/kg); lung fibrosis model group with intratracheal injection of 1.5 mg/mL bleomycin solution (prepared with saline, 3 mg/kg); EXOs1 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 μg/250 μL, given by tail vein injection on the next day after modeling); and EXOs2 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 μg/250 μL, given by tail vein injection on the 10th day after modeling). At 21 days after modeling, pulmonary index, lung tissue pathology and collagen deposition in the mice were assessed using HE staining and Masson staining. The expression level of TGF-β1 was detected using ELISA, and vimentin, E-cadherin and phosphorylated Smad2/3 (p-Smad2/3) were detected using immunohistochemical staining. CCK8 assay was used to evaluate the effect of hUCMSCEXOs on the viability of A549 cells, and Western blotting was used to detect the expression levels of p-Smad2/3, vimentin, and E-cadherin in the cells.
RESULTS:Compared with those in the model group, the mice treated with hUCMSC-EXOs showed significantly reduced the pulmonary index ( < 0.05), collagen deposition, lung tissue pathologies, lowered expressions of TGF-β1 ( < 0.05), vimentin, and p-Smad2/3 and increased expression of E-cadherin. hUCMSC-EXOs given on the second day produced more pronounced effect than that given on the 11th day ( < 0.05). CCK8 assay results showed that hUCMSC-EXOs had no toxic effects on A549 cells ( > 0.05). Western blotting results showed that hUCMSC-EXOs treatment significantly increased the expression of E-cadherin and decreased the expressions of p-Smad2/3 and vimentin in the cells.
CONCLUSIONS:hUCMSC-EXOs can alleviate pulmonary fibrosis in mice by inhibiting epithelialmesenchymal transition activated by the TGF-β1/Smad2/3 signaling pathway, and the inhibitory effect is more obvious when it is administered on the second day after modeling.
