The therapeutic effect of exosomal lncRNA MSTRG.91634.7 on mitochondrial dysfunction during SiO2-induced lung fibrosis

Jiaqi Ban; Qi Zhang; Shuai Chang; Huiyan Qu; Fangwei Liu

doi:10.1016/j.intimp.2023.110508

The therapeutic effect of exosomal lncRNA MSTRG.91634.7 on mitochondrial dysfunction during SiO₂-induced lung fibrosis

Int Immunopharmacol. 2023 Aug:121:110508. doi: 10.1016/j.intimp.2023.110508. Epub 2023 Jun 18.

Authors

Jiaqi Ban¹, Qi Zhang², Shuai Chang², Huiyan Qu², Fangwei Liu³

Affiliations

¹ School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou 550025, China; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
² Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
³ Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China; Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China. Electronic address: fwliu@cmu.edu.cn.

PMID: 37339568
DOI: 10.1016/j.intimp.2023.110508

Abstract

Long-term silica (SiO₂) exposure led to irreversible lung fibrosis, in which epithelial-mesenchymal transition (EMT) played an essential role. A novel lncRNA MSTRG.91634.7 in the peripheral exosomes of silicosis patients was reported in our previous study, which could remold the pathological process of silicosis. However, whether its regulatory role on the development of silicosis was related to EMT process is unclear, and its mechanism remains to be further studied. In this study, up-regulating lncRNA MSTRG91634.7 restricted SiO₂-activated EMT and restored mitochondrial homeostasis binding to PINK1 in vitro. Moreover, overexpressing PINK1 could inhibit SiO₂-activated EMT in pulmonary inflammation and fibrosis in mice. Meanwhile, PINK1 contributed to restoring the SiO₂-induced mitochondrial dysfunction in mice lung. Our results revealed that exosomal lncRNA MSTRG.91634.7 from macrophages could restore mitochondrial homeostasis to restrict the SiO₂-activated EMT by binding to PINK1 during pulmonary inflammation and fibrosis due to SiO₂ exposure.

Keywords: Epithelial-mesenchymal transition; Exosome; Mitochondrial dysfunction; PTEN-induced putative kinase 1; Pulmonary interstitial fibrosis; long non-coding RNA.

MeSH terms

Animals
Epithelial-Mesenchymal Transition
Fibrosis
Lung / pathology
Mice
Protein Kinases / metabolism
Pulmonary Fibrosis* / chemically induced
RNA, Long Noncoding* / genetics
Silicon Dioxide
Silicosis* / metabolism

Substances

Silicon Dioxide
RNA, Long Noncoding
Protein Kinases