{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:43:53Z","timestamp":1768801433604,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Necroptosis is an emerging cell death pathway that allows cells to undergo \u201ccellular suicide\u201d in a caspase\u2010independent manner. We investigated the fate of hepatic stellate cells (HSCs) under necroptotic stimuli.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>The RNA level of mixed lineage kinase domain\u2010like protein (MLKL) is higher in patients with non\u2010alcoholic fatty liver disease than in healthy controls. Hepatic fibrosis was significantly lower in MLKL\u2010KO bile duct ligation (KO\u2010BDL) mice than in wild\u2010type\u2010BDL mice. Necroptotic stimuli caused the death of HT\u201029 and U937 cells. However, necroptotic stimuli activate HSCs instead of inducing cell death. MLKL inhibitors attenuated fibrogenic changes in HSCs during necroptosis. Unlike HT\u201029 and U937 cells, MLKL phosphorylation and oligomerization were not observed during necroptosis in HSCs. RNA sequencing showed that NF\u2010\u03baB signaling\u2010related genes were upregulated in HSCs following necroptotic stimulation. Necroptotic stimuli in HSCs increased the nuclear expression of NF\u2010\u03baB, which decreased after MLKL inhibitor treatment. Induction of necroptosis in HSCs led to autophagosome activation and formation, which were attenuated by MLKL inhibitor treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HSCs avoid necroptosis due to the absence of MLKL phosphorylation and oligomerization and are activated through autophagosome and NF\u2010\u03baB pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.16368","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:13:53Z","timestamp":1697073233000},"page":"2206-2214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hepatic stellate cells activate and avoid death under necroptosis stimuli: Hepatic fibrosis during necroptosis"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2864-7677","authenticated-orcid":false,"given":"Ju Hee","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-9108","authenticated-orcid":false,"given":"Waqar Khalid","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Pak\u2010Austria Fachhochschule: Institute of Applied Sciences and Technology  Haripur Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2587-4743","authenticated-orcid":false,"given":"Hye Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Biomedical Science and Engineering Hanyang University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9635-2921","authenticated-orcid":false,"given":"Seung Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Biomedical Science and Engineering Hanyang University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5422-6107","authenticated-orcid":false,"given":"A Hyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Biomedical Science and Engineering Hanyang University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0907-1370","authenticated-orcid":false,"given":"Gye Ryeol","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Biomedical Science and Engineering Hanyang University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0474-048X","authenticated-orcid":false,"given":"Eileen L.","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine Hanyang University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2875-6139","authenticated-orcid":false,"given":"Dae Won","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Graduate School of Biomedical Science and Engineering Hanyang University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.021"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.031"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28676"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140732"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201403856"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11869"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26200"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6893"},{"key":"e_1_2_7_10_1","article-title":"Differential role of MLKL in alcohol\u2010associated and non\u2010alcohol\u2010associated fatty liver diseases in mice and humans. 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