MiR-421 mediates PM_2.5-induced endothelial dysfunction via crosstalk between bronchial epithelial and endothelial cells

Abstract

Objective

PM_2.5 is closely linked to vascular endothelial injury and has emerged as a major threat to human health. Our previous research indicated that exposure to PM_2.5 induced an increased release of miR-421 from the bronchial epithelium. However, the role of miR-421 in PM_2.5-induced endothelial injury remains elusive.

Materials and methods

We utilized a subacute PM_2.5-exposure model in mice in vivo and an acute injury cell model in vitro to simulate PM_2.5-associated endothelial injury. We also used quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry to investigate the role of miR-421 in PM_2.5-induced endothelial injury.

Results

Our findings reveal that inhibition of miR-421 attenuated PM_2.5-induced endothelial injury and hypertension. Mechanistically, miR-421 inhibited the expression of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein endothelial cells and upregulated the expression of the downstream molecule inducible nitric oxide synthase (iNOS), thereby exacerbating PM_2.5-induced endothelial injury.

Conclusions

Our results indicate that PM_2.5 exposure facilitates crosstalk between bronchial epithelial and endothelial cells via miR-421/ACE2/iNOS signaling pathway, mediating endothelial damage and hypertension. MiR-421 inhibition may offer a new strategy for the prevention and treatment of PM_2.5-induced vascular endothelial injury.

Keywords:

• PM_2.5
• endothelial injury
• hypertension
• MiR-421
• cross-talk

Authors’ contributions

Investigation and writing, Y.C., M.Z., J.X. and M.S.; formal analysis and data curation, Z.X., Y.J. and Z.P.; conceptualization, project administration and supervision, T.W. and H.W. All authors have read and agreed to the published version of the manuscript.

Data availability statement

All other data are included within the article or available from the authors on request.

Disclosure statement

The authors report there are no competing interests to declare.

Institutional review board statement

The animal study protocol was approved by the Ethics Committee of Shanghai University.

Additional information

Funding

This work was supported by the [National Natural Science Foundation of China #1] under Grant [number 82000253]; [National Natural Science Foundation of China #2] under Grant [number 82370277]; and [Science and Technology Commission of Shanghai #3] under Grant [number 20YF1414000]; and [Science and Technology Commission of Shanghai #4] under Grant [number 23ZR1422900] and ['Chenguang Program’ of Shanghai Education Development Foundation, and Shanghai Municipal Education Commission #5] under Grant [number 20CG46]