PPARγ activation ameliorates PM2.5-induced renal tubular injury by inhibiting ferroptosis and epithelial–mesenchymal transition

Autor: Chien-Hung Lin, Wen-Sheng Liu, Chuan Wan, Hsin-Hui Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Current Research in Toxicology, Vol 7, Iss , Pp 100189- (2024)
Druh dokumentu: article
ISSN: 2666-027X
DOI: 10.1016/j.crtox.2024.100189
Popis: Exposure to fine particulate matter (PM2.5) has been associated with the development and progression of renal disease. Peroxisome proliferator-activated receptor gamma (PPARγ), a key transcription factor involved in inflammation as well as lipid and glucose metabolism, helps maintain the integrity of tubular epithelial cells. However, the precise role of PPARγ in PM2.5-induced tubular injury remains unclear. In this study, we investigated the regulatory effects of PPARγ on PM2.5-induced ferroptotic stress and epithelial–mesenchymal transition (EMT) in tubular (HK-2) cells. We found that downregulation of PPARγ expression was correlated with EMT in PM2.5-exposed cells. Pretreatment with the PPARγ agonist 15d-PGJ2 protected the cells from EMT by reducing ferroptotic stress, whereas that with the PPARγ antagonist GW9662 promoted EMT. Furthermore, pretreatment with ferrostatin-1 (Fer-1) significantly prevented PM2.5-induced EMT and downregulation of PPARγ expression. Notably, overexpression of PPARγ blocked PM2.5-induced downregulation of E-cadherin and GPX4 expression and upregulation of α-SMA expression. This study highlights the complex associations of PPARγ with ferroptosis and EMT in PM2.5-exposed tubular cells. Our findings suggest that PPARγ activation confers protection against PM2.5-induced renal injury.
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