{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:04:58Z","timestamp":1792782298082,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2009,10,28]],"date-time":"2009-10-28T00:00:00Z","timestamp":1256688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes of Health (NIH) RO1","award":["DK063275"],"award-info":[{"award-number":["DK063275"]}]},{"name":"National Institutes of Health (NIH) RO1","award":["HL080130"],"award-info":[{"award-number":["HL080130"]}]},{"name":"National Institutes of Health (NIH) RO1","award":["T32 HL07734"],"award-info":[{"award-number":["T32 HL07734"]}]},{"name":"July Henry Fund"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The nuclear factor-\u03baB inhibitory protein A20 demonstrates hepatoprotective abilities through combined antiapoptotic, anti-inflammatory, and pro-proliferative functions. Accordingly, overexpression of A20 in the liver protects mice from toxic hepatitis and lethal radical hepatectomy, whereas A20 knockout mice die prematurely from unfettered liver inflammation. The effect of A20 on oxidative liver damage, as seen in ischemia\/reperfusion injury (IRI), is unknown. In this work, we evaluated the effects of A20 upon IRI using a mouse model of total hepatic ischemia. Hepatic overexpression of A20 was achieved by recombinant adenovirus (rAd.)-mediated gene transfer. Although only 10%-25% of control mice injected with saline or the control rAd.\u03b2 galactosidase survived IRI, the survival rate reached 67% in mice treated with rAd.A20. This significant survival advantage in rAd.A20-treated mice was associated with improved liver function, pathology, and repair potential. A20-treated mice had significantly lower bilirubin and aminotransferase levels, decreased hemorrhagic necrosis and steatosis, and increased hepatocyte proliferation. A20 protected against liver IRI by increasing hepatic expression of peroxisome proliferator-activated receptor alpha (PPAR\u03b1), a regulator of lipid homeostasis and of oxidative damage. A20-mediated protection of hepatocytes from hypoxia\/reoxygenation and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      -mediated necrosis was reverted by pretreatment with the PPAR\u03b1 inhibitor MK886. In conclusion, we demonstrate that PPAR\u03b1 is a novel target for A20 in hepatocytes, underscoring its novel protective effect against oxidative necrosis. By combining hepatocyte protection from necrosis and promotion of proliferation, A20-based therapies are well-poised to protect livers from IRI, especially in the context of small-for-size and steatotic liver grafts. Liver Transpl 15:1613\u20131621, 2009. \u00a9 2009 AASLD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lt.21879","type":"journal-article","created":{"date-parts":[[2009,10,29]],"date-time":"2009-10-29T16:42:57Z","timestamp":1256834577000},"page":"1613-1621","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":40,"title":["A20 protects mice from lethal liver ischemia\/reperfusion injury by increasing peroxisome proliferator-activated receptor-\u03b1 expression"],"prefix":"10.1097","volume":"15","author":[{"given":"Haley E.","family":"Ramsey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleide G.","family":"Da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Longo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Csizmadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Studer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virendra I.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Damrauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Siracuse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soizic","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Ferran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-33-20250326","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1001\/archsurg.1996.01430160100022","article-title":"Multiplesystem organ damage resulting from prolonged hepatic inflow interruption.","volume":"131","author":"Liu","year":"1996","journal-title":"Arch Surg"},{"key":"R2-33-20250326","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/00007890-199808150-00005","article-title":"Early allograft dysfunction after liver transplantation: a definition and predictors of outcome. 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