{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:24:33Z","timestamp":1792160673263,"version":"4.4.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:p>Hepatic ischemic-reperfusion injury (HIRI) is considered a risk factor for clinical acute kidney injury (AKI). However, HIRI's impact on renal tubular cell homeostasis and subsequent injury responses remain ill-defined. To explore this issue, 30\u201345 min of partial HIRI was induced in CD-1 mice. Sham-operated or normal mice served as controls. Renal changes and superimposed injury responses (glycerol-induced AKI; endotoxemia) were assessed 2\u201318 h later. HIRI induced mild azotemia (blood urea nitrogen \u223c45 mg\/dl) in the absence of renal histologic injury or proteinuria, implying a \u201cprerenal\u201d state. However, marked renal cortical, and isolated proximal tubule, cytoprotective \u201cstress protein\u201d gene induction (neutrophil gelatinase-associated lipocalin, heme oxygenase-1, hemopexin, hepcidin), and increased Toll-like receptor 4 (TLR4) expression resulted (protein\/mRNA levels). Ischemia caused release of hepatic heme-based proteins (e.g., cytochrome c) into the circulation. This corresponded with renal cortical oxidant stress (malondialdehyde increases). That hepatic derived factors can evoke redox-sensitive \u201cstress protein\u201d induction was implied by the following: peritoneal dialysate from HIRI mice, soluble hepatic extract, or exogenous cytochrome c each induced the above stress protein(s) either in vivo or in cultured tubule cells. Functional significance of HIRI-induced renal \u201cpreconditioning\u201d was indicated by the following: 1) HIRI conferred virtually complete morphologic protection against glycerol-induced AKI (in the absence of hyperbilirubinemia) and 2) HIRI-induced TLR4 upregulation led to a renal endotoxin hyperresponsive state (excess TNF-\u03b1\/MCP-1 gene induction). In conclusion, HIRI can evoke \u201crenal preconditioning,\u201d likely due, in part, to hepatic release of pro-oxidant factors (e.g., cytochrome c) into the systemic circulation. The resulting renal changes can impact subsequent AKI susceptibility and TLR4 pathway-mediated stress.<\/jats:p>","DOI":"10.1152\/ajprenal.00378.2014","type":"journal-article","created":{"date-parts":[[2014,7,31]],"date-time":"2014-07-31T07:13:37Z","timestamp":1406790817000},"page":"F856-F868","source":"Crossref","is-referenced-by-count":16,"title":["Acute hepatic ischemic-reperfusion injury induces a renal cortical \u201cstress response,\u201d renal \u201ccytoresistance,\u201d and an endotoxin hyperresponsive state"],"prefix":"10.1152","volume":"307","author":[{"given":"Richard A.","family":"Zager","sequence":"first","affiliation":[{"name":"The Fred Hutchinson Cancer Research Center, Seattle, Washington; and University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali C. M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"The Fred Hutchinson Cancer Research Center, Seattle, Washington; and University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten B.","family":"Frostad","sequence":"additional","affiliation":[{"name":"The Fred Hutchinson Cancer Research Center, Seattle, Washington; and University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-012-2386-3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114656"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5386.810"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1978.31"},{"key":"B5","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1681\/ASN.V4101735","volume":"4","author":"Epstein M","year":"1994","journal-title":"J Am Soc Nephrol"},{"key":"B6","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1681\/ASN.V661655","volume":"6","author":"Fink JC","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1988.255.3.F450"},{"key":"B8","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1681\/ASN.V5111853","volume":"5","author":"Green J","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01000211"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.003"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2005.09.003"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.0600031047.x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e328332f69e"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.02.006"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/BF00584322"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-515957"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2013.837264"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23056"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007121368"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115847"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0624com"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2013.11.2715"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr387"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2014.01.004"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.6"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2174\/1871527311312050006"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs067"},{"key":"B28","first-page":"789","volume":"44","author":"Tajiri K","year":"1997","journal-title":"Hepatogastroenterology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199605303342207"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs380"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1978.87"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00654.2010"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e31826359d0"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2012.96"},{"key":"B35","first-page":"16.","volume-title":"Comprehensive Clinical Nephrology","author":"Woolfson RG","year":"2000"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1988.13"},{"key":"B37","first-page":"798","volume":"59","author":"Zager RA","year":"1988","journal-title":"Lab Invest"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.48"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00638.x"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011121147"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00426.2012"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066776"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098380"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.72.4.837"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00023.2005"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000022"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00237.2006"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00381.2009"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00072.2006"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00168.2012"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00378.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:03:01Z","timestamp":1649829781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00378.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,10,1]]}},"alternative-id":["10.1152\/ajprenal.00378.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00378.2014","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,1]]}}}