{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:28:03Z","timestamp":1790400483844,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK98414 and R56 DK112768"],"award-info":[{"award-number":["R01 DK98414 and R56 DK112768"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Overdose of acetaminophen (APAP) is the major cause of acute liver failure (ALF) in the Western world with very limited treatment options. Previous studies from our groups and others have shown that timely activation of liver regeneration is a critical determinant of transplant-free survival of APAP-induced ALF patients. Here, we report that hepatocyte-specific deletion of Yes-associated protein (Yap), the downstream mediator of the Hippo Kinase signaling pathway results in faster recovery from APAP-induced acute liver injury. Initial studies performed with male C57BL\/6J mice showed a rapid activation of Yap and its target genes within first 24\u2009h after APAP administration. Treatment of hepatocyte-specific Yap knockout (Yap-KO) mice with 300\u2009mg\/kg APAP resulted in equal initial liver injury but a significantly accelerated recovery in Yap-KO mice. The recovery was accompanied by significantly rapid hepatocyte proliferation supported by faster activation of Wnt\/\u03b2-catenin pathway. Furthermore, Yap-KO mice had significantly earlier and higher pro-regenerative inflammatory response following APAP overdose. Global gene expression analysis indicated that Yap-KO mice had a robust activation of transcription factors involved in response to endoplasmic reticulum stress (XBP1) and maintaining hepatocyte differentiation (HNF4\u03b1). In conclusion, these data indicate that inhibition of Yap in hepatocytes results in rapid recovery from APAP overdose due to an earlier activation of liver regeneration.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab115","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T19:20:24Z","timestamp":1632165624000},"page":"276-285","source":"Crossref","is-referenced-by-count":18,"title":["Hepatocyte-Specific Deletion of Yes-Associated Protein Improves Recovery From Acetaminophen-Induced Acute Liver Injury"],"prefix":"10.1093","volume":"184","author":[{"given":"Samikshya","family":"Poudel","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-9497","authenticated-orcid":false,"given":"Diego Paine","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Bhushan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Michael W","family":"Manley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumedha","family":"Gunewardena","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-6980","authenticated-orcid":false,"given":"Hartmut","family":"Jaeschke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udayan","family":"Apte","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"2021120108285081500_kfab115-B1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/toxsci\/69.2.448","article-title":"Upregulated promitogenic signaling via cytokines and growth factors: Potential mechanism of robust liver tissue repair in calorie-restricted rats upon toxic challenge","volume":"69","author":"Apte","year":"2002","journal-title":"Toxicol. 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