miR-629-3p inhibits fine particulate matter exposure-induced lung function decline: results from the two-stage population study and in vitro study

Min Zhou; Xiaojie You; Jiake Zhang; Zi Ye; Jiahao Song; Bingdong Chen; Lieyang Fan; Jixuan Ma; Shijie Yang; Man Cheng; Weihong Chen

doi:10.1016/j.envpol.2024.125535

miR-629-3p inhibits fine particulate matter exposure-induced lung function decline: results from the two-stage population study and in vitro study

Environ Pollut. 2024 Dec 17:125535. doi: 10.1016/j.envpol.2024.125535. Online ahead of print.

Authors

Min Zhou¹, Xiaojie You¹, Jiake Zhang¹, Zi Ye¹, Jiahao Song¹, Bingdong Chen¹, Lieyang Fan¹, Jixuan Ma¹, Shijie Yang², Man Cheng³, Weihong Chen⁴

Affiliations

¹ Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei 430079, China.
³ Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
⁴ Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: [email protected].

PMID: 39701361
DOI: 10.1016/j.envpol.2024.125535

Abstract

MiRNAs were reported to play crucial roles in the pathogenesis of health damage caused by environmental pollutants. However, its potential role in fine particulate matter (PM_2.5) exposure-induced lung function decline has rarely been elucidated. The present study was developed to profile specific miRNAs that were related to both PM_2.5 exposure and lung function decline, and to investigate the regulating role in PM_2.5 exposure-induced lung injury. Based on the Wuhan-Zhuhai cohort, in the discovery stage, plasma miRNA profiling for PM_2.5 exposure was conducted through next-generation sequencing among 60 participants with 120 observations in a repeated-measures design. Plasma miRNA profiling for lung function decline was conducted among 10 pairs of lung function decline incident cases and matched healthy controls. In the validating stage, miR-629-3p was selected from miRNAs that were related to both PM_2.5 exposure and lung function decline, and was measured by quantitative real-time PCR among 475 residents to validate its association with PM_2.5 exposure as well as lung function. In vitro, PM_2.5-treated A549 and BEAS-2B cell models and miR-629-3p mimic/inhibitor models were used to explore the role and underlying mechanism of miR-629-3p on epithelial-mesenchymal transition (EMT) induced by PM_2.5 exposure. The two-stage population study found a negative association between personal PM_2.5 exposure and plasma miR-629-3p, while a positive association between miR-629-3p and lung function. In vitro, PM_2.5 treatment stimulated the expressions of EMT-related factors, accompanied by the activation of TGF-β1/TGF-βR1 signal pathway. Overexpression of miR-629-3p could inhibit PM_2.5-induced TGF-βR1 expression and alleviate EMT process. And inhibition of miR-629-3p could promote TGF-βR1 expression and aggravate EMT process. In conclusion, miR-629-3p may alleviate the lung injury induced by PM_2.5 exposure through inhibiting TGF-β1/TGF-βR1 pathway.

Keywords: TGF-β1/TGF-βR1 pathway; fine particulate matter; lung injury; miR-629-3p; microRNA.