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However, its molecular mechanisms remain unclear. This study integrated bioinformatics, network pharmacology, and molecular docking to identify the epithelial growth factor receptor (EGFR) as a key target of quercetin. In folic acid (FA)-induced CKD mice, quercetin decreased renal fibrosis (reducing [Formula: see text]-SMA, collagen I, and fibronectin), suppressed ferroptosis markers (including iron accumulation, malondialdehyde [MDA] levels, and acyl-CoA synthetase long-chain family member 4 [ACSL4] expression), and downregulated EGFR.\u00a0In FA-stimulated HK-2 cells, quercetin inhibited epithelial-mesenchymal transition (by decreasing N-cadherin and fibronectin) and ferroptosis (by lowering iron, MDA, and ACSL4) while suppressing EGFR expression. Pharmacological inhibition and genetic knockout of EGFR in HK-2 cells confirmed that EGFR blockade alleviated FA-induced renal fibrosis and ferroptosis. These findings demonstrate that quercetin mitigates FA-induced renal fibrosis by inhibiting tubular epithelial ferroptosis via the EGFR\/ACSL4 signaling axis, and thus highlights its therapeutic potential in CKD.<\/jats:p>","DOI":"10.1142\/s0192415x25500715","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T02:32:50Z","timestamp":1754533970000},"page":"1913-1931","source":"Crossref","is-referenced-by-count":11,"title":["Quercetin Alleviates Folic Acid-Induced Renal Fibrosis by Inhibiting Tubular Epithelial Cell Ferroptosis via EGFR\/ACSL4 Pathway"],"prefix":"10.1142","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4459-1461","authenticated-orcid":false,"given":"Xian-Li","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518000, 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