{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:47:57Z","timestamp":1789069677634,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Heart failure induced by sepsis is considered one of the foremost contributors to mortality in intensive care unit (ICU) patients. However, the molecular mechanism of myocardial damage in sepsis has not been fully elucidated at present. TNF receptor\u2010associated factor\u20102 and Nck\u2010interacting protein kinase (TNIK) are members of the germinal center kinase superfamily. TNIK exhibits a pivotal role as a conserved modulator of glucose and lipid homeostasis. Here, we aimed to investigate the potential direct roles of TNIK and whether TNIK exerts anti\u2010septic myocardial damage by regulating the NLRP3 pathway. We initially revealed that TNIK was the crucial involvement of septic myocardial injury. Subsequently, we constructed a cecal ligation and puncture (CLP) mouse model and employed LPS\u2010induced injury in HL\u20101 cardiomyocytes. Our observations revealed an upregulation of TNIK levels in both CLP\u2010injured mice and LPS\u2010treated HL\u20101 cells. However, TNIK inhibitor TNIK\u2010IN\u20107 or siRNA attenuated cardiomyocyte LPS injury. Especially, TNIK siRNA can significantly downregulate TNIK as well as decrease NLRP3 and IL\u20101\u03b2 mRNA and protein levels, though the explicit molecular mechanisms of TNIK\u2010NLRP3 in septic myocardial require further investigation. Together, our investigation presents novel evidence suggesting TNIK as a potential therapeutic target for the prevention and therapeutic intervention in sepsis\u2010induced cardiomyopathy.<\/jats:p>","DOI":"10.1002\/jcp.70027","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T07:58:27Z","timestamp":1743667107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pleiotropic Role of TNIK in Sepsis\u2010Induced Cardiomyopathy"],"prefix":"10.1002","volume":"240","author":[{"given":"Wenwen","family":"Yang","sequence":"first","affiliation":[{"name":"Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine Northwest University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine Northwest University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangrui","family":"Lei","sequence":"additional","affiliation":[{"name":"Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine Northwest University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmin","family":"Chen","sequence":"additional","affiliation":[{"name":"Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine Northwest University Xi'an China"},{"name":"Department of Cardiology, Affiliated Hospital Yan'an University Yan'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanle","family":"Yan","sequence":"additional","affiliation":[{"name":"Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine Northwest University Xi'an 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