Lichun Zhang1, Qiuhe Li1, Zhenning Liu1, Yu Wang1, Min Zhao1. 1. Department of Emergency, Shengjing Hospital Affiliated to China Medical University No. 36 Sanhao Street, Heping District, Shenyang 110004, Liaoning Province, China.
Abstract
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.
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 ratpulmonary 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.
Entities:
Keywords:
Bone marrow derived mesenchymal stem cells; Muc5b and ERK/MAPK signaling pathways; acute lung injury; paraquat poisoning
Authors: Andrew A Monte; Hao Sun; Anna Malin Rapp-Olsson; Fahim Mohamed; Indika Gawarammana; Nicholas A Buckley; Christopher M Evans; Ivana V Yang; David A Schwartz Journal: Am J Respir Crit Care Med Date: 2018-03-01 Impact factor: 21.405