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

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) exposure-induced lung function decline has rarely been elucidated. The present study was developed to profile specific miRNAs that were related to both PM exposure and lung function decline, and to investigate the regulating role in PM exposure-induced lung injury. Based on the Wuhan-Zhuhai cohort, in the discovery stage, plasma miRNA profiling for PM 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 exposure and lung function decline, and was measured by quantitative real-time PCR among 475 residents to validate its association with PM exposure as well as lung function. In vitro, PM-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 exposure. The two-stage population study found a negative association between personal PM exposure and plasma miR-629-3p, while a positive association between miR-629-3p and lung function. In vitro, PM 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-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 exposure through inhibiting TGF-β1/TGF-βR1 pathway.