{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:34:47Z","timestamp":1788518087122,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2019MH029"],"award-info":[{"award-number":["ZR2019MH029"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As a novel nuclear factor E2\u2010related factor 2 (NRF2) activator, the itaconate has shown significant therapeutic potential for oxidative stress diseases. However, its role in Vohwinkel syndrome in relation to the <jats:italic>gap junction protein beta 2<\/jats:italic> (<jats:italic>GJB2<\/jats:italic>) mutation is still unclear. This study aimed at investigating the effect of 4\u2010octyl itaconate (OI) on HaCaT and D66H cells and clarify its potential mechanism in vitro. The optimal concentration and treatment time of OI on HaCaT cells and D66H cells were determined by CCK\u20108 and LDH experiments. The effect of OI on cell proliferation was detected by EdU staining and FACS analysis of PI, while the apoptosis was evaluated by TUNEL staining and FACS analysis of Annexin V. The ROS staining was performed, and the levels of SOD, MDA, GSH and GSH\/GSSG were detected to evaluate the effect of OI on oxidative damage induced by D66H\u2010type mutation. CO\u2010IP, Western blot, immunofluorescence and qPCR analyses were employed to detect the activation of KEAP1\u2010NRF2\u2010GCLC\/HO\u20101 pathway by OI. Finally, sh\u2010NRF2 was used to confirm the activation of this pathway by OI. Results showed that OI could improve the cell viability decreased by <jats:italic>GJB2<\/jats:italic> gene mutation by regulating the balance between cell growth and apoptosis induced by oxidative damage. Furthermore, this alleviation process was regulated by the KEAP1\u2010NRF2\u2010HO\u20101\/GCLC pathway. In conclusion, OI could improve the viability of HaCaT and D66H cells via regulating the KEAP1\u2010NRF2\u2010GCLC\/HO\u20101 pathway, which provided a wide spectrum of potential targets for effective therapeutic treatments of Vohwinkel syndrome in the clinic.<\/jats:p>","DOI":"10.1111\/jcmm.17708","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T06:49:49Z","timestamp":1678776589000},"page":"962-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["4\u2010octyl itaconate improves the viability of D66H cells by regulating the KEAP1\u2010NRF2\u2010GCLC\/HO\u20101 pathway"],"prefix":"10.1111","volume":"27","author":[{"given":"Yanrui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Dermatology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan China"},{"name":"Department of Dermatology, Shandong Provincial Hospital, Cheeloo 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