Protective role of mesenchymal stem cells transfected with miRNA-378a-5p in phosgene inhalation lung injury
| Autor: | Yuedong Tang, Daikun He, Lin Zhang, Yubei Qu, Jie Shen, Yiru Shao, Ning Xu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Acute Lung Injury Biophysics Lung injury Mesenchymal Stem Cell Transplantation Transfection Biochemistry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Western blot White blood cell microRNA Medicine Animals Secretion Phosgene Molecular Biology Cells Cultured medicine.diagnostic_test business.industry Hepatocyte Growth Factor Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Rats Up-Regulation MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Hepatocyte growth factor business medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 530(1) |
| ISSN: | 1090-2104 |
| Popis: | Phosgene-induced lung injury is an important type of acute lung injury (ALI). Currently, no effective clinical treatment has been developed yet. Our previous study revealed that expressions of 6 miRNAs were significantly increased in phosgene-induced lung injury. The screened miRNA with the most significant effect on hepatocyte growth factor (HGF) expression by mesenchymal stem cells (MSCs) was transfected into MSCs. This study aimed to investigate whether the transfected MSCs had better therapeutic effects than MSCs alone. MSCs were co-cultured with miRNA mimics for 24h and 48h. HGF expression in culture supernatant was detected by ELISA. HGF expression in MSCs was detected by Western blot after being co-cultured with the selected miRNA inhibitor. The transfected MSCs were given to rats suffering from phosgene-induced lung injury. Expressions of TNF-α, IL-6, IL-1β and IL-10, were assayed by ELISA. SP-C mRNA level was tested by RT-PCR. VE-CAD expression was tested by Western blot. We found that miRNA-378a-5p most increased HGF expression among the six miRNAs. After transfection of MSCs with miRNA-378a-5p inhibitor, HGF expression was decreased. Compared with untreated MSCs, MSCs transfected with miRNA-378a-5p exhibited more significant decreases in lung injury score, white blood cell count and protein content while restoring respiratory indexes. Meanwhile, expressions of TNF-α, IL-6, IL-1β were decreased while those of IL-10, SP-C and VE-cadherin were increased. In conclusion, MSCs transfected with miRNA-378a-5p were more effective in treating phosgene-induced lung injury by repairing the secretion of alveolar epithelial cells and improving the permeability of vascular endothelial cells compared with MSCs alone. |
| Databáze: | OpenAIRE |
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