Bone marrow-derived mesenchymal stem cells attenuate silica-induced pulmonary fibrosis by inhibiting apoptosis and pyroptosis but not autophagy in rats

Qiuyan Zhao; Changfu Hao; Jingjing Wei; Ruoxuan Huang; Chao Li; Wu Yao

doi:10.1016/j.ecoenv.2021.112181

Bone marrow-derived mesenchymal stem cells attenuate silica-induced pulmonary fibrosis by inhibiting apoptosis and pyroptosis but not autophagy in rats

Ecotoxicol Environ Saf. 2021 Apr 10:216:112181. doi: 10.1016/j.ecoenv.2021.112181. Online ahead of print.

Authors

Qiuyan Zhao¹, Changfu Hao¹, Jingjing Wei¹, Ruoxuan Huang¹, Chao Li¹, Wu Yao²

Affiliations

¹ Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
² Department of Occupational Health and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: yaowu@zzu.edu.cn.

PMID: 33848736
DOI: 10.1016/j.ecoenv.2021.112181

Abstract

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on silica-induced lung fibrosis in a rat model. Thirty SD rats were randomly divided into three groups: control group, silica group, and BMSC group (n = 10 rats per group). BMSCs were injected successively into rats on the 14th, 28th, and 42nd days after silica exposure. All rats were sacrificed 56 days after silica exposure. We detected the pathological and fibrotic changes, apoptosis, autophagy, and pyroptosis in their lung tissue by histopathological examination, hydroxyproline content assays, real-time quantitative polymerase chain reactions, western blot assays, immunohistochemistry staining, immunofluorescence staining, and enzyme-linked immunosorbent assays. We found that BMSCs significantly relieved lung inflammatory infiltrates, collagen deposition, hydroxyproline content, and the mRNA and protein levels of collagen 1 and fibronectin. Compared to the silica group, in the BMSC group, apoptosis-associated proteins, including cleaved caspase 3 and Bax, were significantly downregulated, and Bcl-2/Bax was significantly upregulated; pyroptosis-related proteins, including Nlrp3, cleaved caspase 1, IL-1β, and IL-18, were significantly reduced. However, the BMSCs had no significant impact on autophagy-related proteins, including Beclin 1, P62, and LC3. In summary, BMSCs protected lung tissue against severe fibrosis by inhibiting apoptosis and pyroptosis but not autophagy.

Keywords: Apoptosis; Autophagy; Bone marrow-derived mesenchymal stem cell; Pulmonary fibrosis; Pyroptosis.