{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:33:32Z","timestamp":1787315612466,"version":"build-2736575974"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600533 U1904134"],"award-info":[{"award-number":["81600533 U1904134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011447","name":"Science and Technology Department of Henan Province","doi-asserted-by":"publisher","award":["212102310189"],"award-info":[{"award-number":["212102310189"]}],"id":[{"id":"10.13039\/501100011447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019331","name":"Henan Medical Science and Technique Foundation","doi-asserted-by":"publisher","award":["SBGJ2020002070"],"award-info":[{"award-number":["SBGJ2020002070"]}],"id":[{"id":"10.13039\/501100019331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Backgroud:<\/jats:bold>\n                    Ferroptosis is a form of regulated cell death in ischemia-reperfusion (I\/R) injury models. Acute kidney injury (AKI) induced by I\/R injury can result in cell death, and subcellular structural changes, including expansion of the endoplasmic reticulum (ER), mitochondrial shrinkage, and other morphological changes. Inositol requiring enzyme 1 (IRE1) a proximal ER stress sensor, activates c-Jun NH2-terminal kinases (JNK) in response to ER stress, which is inextricably linked to ER.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Method:<\/jats:bold>\n                    To determine the resulting damage and relationship between ferroptosis and the IRE1\/JNK pathway in AKI, we modeled AKI in I\/R renal injury mice and hypoxia\/reoxygenation (H\/R) HK-2 cells, as\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments, respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    In I\/R renal injury mice, we found that abnormal renal function; damage of renal tubular epithelial cells; activation of the IRE1\/JNK pathway and ferroptosis. Our\n                    <jats:italic>in vitro<\/jats:italic>\n                    study showed a large number of reactive oxygen species and more ferroptotic mitochondria in H\/R HK-2 cells. By inhibiting IRE1\/JNK in I\/R renal injury mice, we observed decreased blood urea nitrogen, creatinine, and tissue injury, compared with the I\/R group, we also found the markers of ferroptosis changed, including decreased 4-hydroxynonenal and increased glutathione peroxidase 4, as well as in H\/R induced IRE1\/JNK knock-down HK-2 cell lines (stable depletion). Furthermore, inhibition of ferroptosis could also attenuate the IRE1\/JNK pathway in mice following I\/R and HK-2 cells following H\/R.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    We observed cross-talk between the IRE1\/JNK pathway and ferroptosis in I\/R or H\/R induced AKI. Our findings suggest that ferroptosis plays an important role in I\/R induced AKI, and that inhibition of the IRE1\/JNK pathway can protect against I\/R induced renal injury by inhibiting ferroptosis. The inhibition of the IRE1\/JNK pathway could therefore be a feasible therapeutic target for treatment of AKI.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.927641","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T08:21:22Z","timestamp":1661502082000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":43,"title":["Inhibition of the IRE1\/JNK pathway in renal tubular epithelial cells attenuates ferroptosis in acute kidney injury"],"prefix":"10.3389","volume":"13","author":[{"given":"Yan","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"H659","DOI":"10.1152\/ajpheart.00452.2017","article-title":"Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes","volume":"314","author":"Baba","year":"2018","journal-title":"Am. 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