Calcitriol/vitamin D receptor system alleviates PM2.5-induced human bronchial epithelial damage through upregulating mitochondrial bioenergetics in association with regulation of HIF-1α/PGC-1α signaling

Chatsirisupachai A.Muanjumpon P.Jeayeng S.Onkoksong T.Pluempreecha M.Soingam T.Panich U.Mahidol University2024-09-292024-09-292024-10-01Environmental Toxicology and Pharmacology Vol.111 (2024)13826689https://repository.li.mahidol.ac.th/handle/20.500.14594/101419PM2.5 exposure causes lung injury by triggering oxidative stress, mitochondrial dysfunction, and modulating HIF-1α signaling. Calcitriol activates VDR, which regulates cellular homeostasis. This study evaluated the protective role of the calcitriol/VDR system in PM2.5-induced damage to BEAS-2B bronchial epithelial cells by reducing oxidative stress, upregulating mitochondrial bioenergetics, and downregulating HIF-1α. We found that the calcitriol/VDR system decreased ROS formation and restored mitochondrial bioenergetics in PM2.5-treated cells. This improvement correlated with reduced HIF-1α nuclear translocation and increased PGC-1α protein and mitochondrial gene expressions. This study is the first to suggest that targeting the calcitriol/VDR system could be a promising pharmacological strategy for mitigating PM2.5-induced lung epithelial damage by promoting mitochondrial bioenergetics and regulating PGC-1α and HIF-1α signaling.Pharmacology, Toxicology and PharmaceuticsEnvironmental ScienceCalcitriol/vitamin D receptor system alleviates PM2.5-induced human bronchial epithelial damage through upregulating mitochondrial bioenergetics in association with regulation of HIF-1α/PGC-1α signalingArticleSCOPUS10.1016/j.etap.2024.1045682-s2.0-8520458045718727077