Abstract | Background: Methods: We constructed a mouse model of bleomycin-induced pulmonary fibrosis. In vitro, the senescence model of BM-MSCs was constructed with hydrogen peroxide and high concentration of N-methyl-D-aspartate (NDMA). The changes in aging-related indexes were detected by senescence associated beta-galactosidase (SA-β-gal) staining, western blot, flow cytometry and real time-PCR. The epithelial-mesenchymal transformation (EMT) changes of mouse lung epithelial cells (MLE-12) co-cultured with senescent BM-MSCs were detected by immunofluorescence and western blotting. Results: We observed that endogenous BM-MSCs senescence occurs during bleomycin-induced pulmonary fibrosis in mice, and the model group had a higher expression level of the NMDAR subunit than the control group. We observed a significant increase in NMDAR subunit expression in a hydrogen peroxide-induced senescent cell model in vitro. BM-MSCs showed senescence-related phenotype and cell cycle arrest after high concentration of NMDA treatment. At the same time, the expression levels of the classic Wingless and int-1 (Wnt) pathway protein β-cantenin and downstream cyclin D1 also changed. In the co-culture of aged BM-MSCs and MLE-12 cells, EMT can be promoted in MLE-12 cells, and MK-801 can partially antagonize the occurrence of EMT. The NMDAR antagonist can partially prevent the above phenomenon. Conclusions: High concentrations of NMDA can promote senescence of BM-MSCs. NMDAR blockers may inhibit endogenous BM-MSCs aging through the WNT signaling pathway, thereby reducing the effect of bleomycin-induced pulmonary fibrosis.
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Authors | Pu Huang, Yan Zhou, Xiao-Hong Li, Yun-Na Zhang, Hai-Peng Cheng, Jia-Feng Fu, Wei Liu, Shaojie Yue, Zi-Qiang Luo |
Journal | Annals of translational medicine
(Ann Transl Med)
Vol. 10
Issue 11
Pg. 642
(Jun 2022)
ISSN: 2305-5839 [Print] China |
PMID | 35813315
(Publication Type: Journal Article)
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Copyright | 2022 Annals of Translational Medicine. All rights reserved. |