{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:57:40Z","timestamp":1774342660439,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the Joint Funds of the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U22A20513"],"award-info":[{"award-number":["U22A20513"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of Sichuan Province","award":["2024NSFSC0297"],"award-info":[{"award-number":["2024NSFSC0297"]}]},{"name":"China Agricultural Research System on Pigs","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Transmissible gastroenteritis virus (TGEV) is a highly pathogenic porcine coronavirus that causes severe gastrointestinal damage in piglets. However, how TGEV affects host iron homeostasis, oxidative stress, and the ferroptosis process remains unclear. This study aimed to investigate the effects of TGEV infection on cellular iron metabolism, oxidative damage, and lipid peroxidation-mediated ferroptosis, as well as to evaluate the potential therapeutic role of retinoic acid (RA). Methods: Using an intestinal epithelial cell model of TGEV infection, we assessed key regulators of iron handling, oxidative stress, lipid peroxidation, and ferroptosis. The expression of ferroportin (FPN) and ferritin (FTH\/L) and the activity of the p62\u2013NRF2\u2013GPX4\/HO-1 antioxidant axis were analyzed, and the effects of exogenous RA treatment on these endpoints were examined. Results: TGEV infection disrupted cellular iron homeostasis by downregulating the expression of ferroportin (FPN) and ferritin (FTH\/L), leading to the accumulation of intracellular free iron, which in turn induced the generation of a large amount of reactive oxygen species (ROS) and ultimately triggered ferroptosis in intestinal epithelial cells. Additionally, TGEV infection significantly inhibited the p62-NRF2-GPX4\/HO-1 antioxidant signaling pathway, further exacerbating the ferroptosis process. Conclusions: This study reveals that ferroptosis is a key pathological mechanism in TGEV-induced intestinal injury and demonstrates that RA exerts a therapeutic effect by regulating iron metabolism and activating the p62-NRF2-GPX4\/HO-1 signaling pathway. These findings provide new theoretical insights for potential intervention strategies targeting virus infection-associated ferroptosis and intestinal damage.<\/jats:p>","DOI":"10.3390\/nu18060994","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:53:34Z","timestamp":1774274014000},"page":"994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Retinoic Acid Alleviates TGEV-Induced Ferroptosis by Activating the p62-NRF2-GPX4\/HO-1 Pathway and Iron Metabolism in Intestinal Epithelial Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Conghui","family":"Yin","sequence":"first","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junning","family":"Pu","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6605-6742","authenticated-orcid":false,"given":"Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianqiang","family":"Che","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huifen","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimin","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1074\/mcp.RA117.000432","article-title":"microRNA-4331 Promotes Transmissible Gastroenteritis Virus (TGEV)-induced Mitochondrial Damage Via Targeting RB1, Upregulating Interleukin-1 Receptor Accessory Protein (IL1RAP), and Activating p38 MAPK Pathway In Vitro","volume":"17","author":"Zhao","year":"2018","journal-title":"Mol. 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