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

Chien-Hung Lin; Wen-Sheng Liu; Chuan Wan; Hsin-Hui Wang

Current Research in Toxicology (Jan 2024)

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

Chien-Hung Lin,
Wen-Sheng Liu,
Chuan Wan,
Hsin-Hui Wang

Affiliations

Chien-Hung Lin: Division of Pediatric Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei 112201, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; College of Science and Engineering, Fu Jen Catholic University, New Taipei 242062, Taiwan
Wen-Sheng Liu: School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; College of Science and Engineering, Fu Jen Catholic University, New Taipei 242062, Taiwan; Division of Nephrology, Department of Medicine, Taipei City Hospital Zhongxing Branch, Taipei 10341, Taiwan; Institute of Food Safety and Health Risk Assessment, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan; Department of Special Education, University of Taipei, Taipei 100234, Taiwan
Chuan Wan: Department of Pediatrics, Taipei City Hospital, Zhongxing Branch, Taipei 10341, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
Hsin-Hui Wang: Division of Pediatric Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei 112201, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Corresponding author at: Division of Pediatric Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, No.201, Sec. 2, Shipai Rd., Beitou District, Taipei, 11201 Taiwan.

Journal volume & issue: Vol. 7
p. 100189

Abstract

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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.

Published in Current Research in Toxicology

ISSN: 2666-027X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Public aspects of medicine: Toxicology. Poisons
Website: https://www.journals.elsevier.com/current-research-in-toxicology

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