The protective effects of bone mesenchymal stem cells on paraquat-induced acute lung injury via the muc5b and ERK/MAPK signaling pathways

摘要

Objective: To evaluate the protective effect of bone mesenchymal stem cells (BMSCs) on paraquat (PQ)-induced acute lung injury (ALI) and investigate the possible underlying mechanisms. Methods: Male Sprague Dawley rats were treated with BMSCs (3 × 10⁶) 1 h after intraperitoneal injection of PQ. The cell apoptosis rate and mitochondrial membrane potential in rat pulmonary alveolar type II epithelial (ATII) cells were quantitated by flow cytometry. IL-17, IL-6, and MUC5B levels in bronchoalveolar lavage fluid (BALF) and ATII culture medium were measured. Lung tissues were collected to determine the wet-to-dry (W/D) ratios and lung injury scores, in addition to the protein and mRNA expression levels of ERK1/2, Bcl-2, Bax, and muc5b. Results: BMSCs had decreased mRNA expression of Muc5b in lung tissue of rats with PQ-induced ALI as shown by RNA-seq. Treatment with BMSCs also alleviated the PQ-induced increases in protein expression in the BALF and reduced the concentration of IL-17, IL-6, and Muc5b in both the BALF and ATII culture medium. In addition, the ATII cell apoptosis rate and mitochondrial membrane potential, as well as the W/D ratios, were decreased by BMSC treatment. Moreover, BMSCs ameliorated the expression levels of Bax mRNA and active caspase-3 proteins and increased Bcl-2 mRNA expression. Furthermore, BMSCs attenuated ERK1/2 activation upon PQ-induced ALI in lung tissue. Conclusion: BMSC therapy can protect against PQ-induced ALI in rats. A possible mechanism is the suppression of the muc5b and ERK/MAPK signaling pathways, resulting in an improvement in the endothelial permeability and a decrease in inflammation and cell apoptosis.