{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:08:33Z","timestamp":1790791713647,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2014,5,3]],"date-time":"2014-05-03T00:00:00Z","timestamp":1399075200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Dig Dis Sci"],"published-print":{"date-parts":[[2014,6]]},"DOI":"10.1007\/s10620-014-3167-6","type":"journal-article","created":{"date-parts":[[2014,5,2]],"date-time":"2014-05-02T05:21:50Z","timestamp":1399008110000},"page":"1197-1206","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["Caspase 3 Inactivation Protects Against Hepatic Cell Death and Ameliorates Fibrogenesis in a Diet-Induced NASH Model"],"prefix":"10.1007","volume":"59","author":[{"given":"Samjhana","family":"Thapaliya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Wree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Povero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Inzaugarat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Berk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Dixon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina G.","family":"Papouchado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel E.","family":"Feldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,5,3]]},"reference":[{"key":"3167_CR1","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1097\/01.mop.0000172816.79637.c5","volume":"17","author":"A Wieckowska","year":"2005","unstructured":"Wieckowska A, Feldstein AE. Nonalcoholic fatty liver disease in the pediatric population: a review. Curr Opin Pediatr. 2005;17:636\u2013641.","journal-title":"Curr Opin Pediatr"},{"key":"3167_CR2","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1056\/NEJMra011775","volume":"346","author":"P Angulo","year":"2002","unstructured":"Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221\u20131231.","journal-title":"N Engl J Med"},{"key":"3167_CR3","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/hep.20466","volume":"40","author":"JD Browning","year":"2004","unstructured":"Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387\u20131395.","journal-title":"Hepatology"},{"key":"3167_CR4","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1542\/peds.2006-1212","volume":"118","author":"JB Schwimmer","year":"2006","unstructured":"Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:1388\u20131393.","journal-title":"Pediatrics"},{"key":"3167_CR5","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1055\/s-0028-1091983","volume":"28","author":"A Wieckowska","year":"2008","unstructured":"Wieckowska A, Feldstein AE. Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Semin Liver Dis. 2008;28:386\u2013395.","journal-title":"Semin Liver Dis"},{"key":"3167_CR6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1053\/j.gastro.2005.04.014","volume":"129","author":"LA Adams","year":"2005","unstructured":"Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113\u2013121.","journal-title":"Gastroenterology"},{"key":"3167_CR7","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/S0016-5085(99)70506-8","volume":"116","author":"CA Matteoni","year":"1999","unstructured":"Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413\u20131419.","journal-title":"Gastroenterology"},{"key":"3167_CR8","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/hep.21327","volume":"44","author":"M Ekstedt","year":"2006","unstructured":"Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865\u2013873.","journal-title":"Hepatology"},{"key":"3167_CR9","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0016-5085(03)00907-7","volume":"125","author":"AE Feldstein","year":"2003","unstructured":"Feldstein AE, Canbay A, Angulo P, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003;125:437\u2013443.","journal-title":"Gastroenterology"},{"key":"3167_CR10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2217\/clp.09.85","volume":"5","author":"SC Cazanave","year":"2010","unstructured":"Cazanave SC, Gores GJ. Mechanisms and clinical implications of hepatocyte lipoapoptosis. Clin Lipidol. 2010;5:71\u201385.","journal-title":"Clin Lipidol"},{"key":"3167_CR11","doi-asserted-by":"crossref","first-page":"6194","DOI":"10.1038\/onc.2008.297","volume":"27","author":"J Li","year":"2008","unstructured":"Li J, Yuan J. Caspases in apoptosis and beyond. Oncogene. 2008;27:6194\u20136206.","journal-title":"Oncogene"},{"key":"3167_CR12","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.2174\/138955708785909899","volume":"8","author":"IT Weber","year":"2008","unstructured":"Weber IT, Fang B, Agniswamy J. Caspases: structure-guided design of drugs to control cell death. Mini Rev Med. 2008;8:1154\u20131162.","journal-title":"Mini Rev Med"},{"key":"3167_CR13","doi-asserted-by":"crossref","first-page":"21777","DOI":"10.1074\/jbc.R800084200","volume":"284","author":"C Pop","year":"2009","unstructured":"Pop C, Salvesen GS. Human caspases: activation, specificity, and regulation. J Biol Chem. 2009;284:21777\u201321781.","journal-title":"J Biol Chem"},{"key":"3167_CR14","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1146\/annurev.biochem.68.1.383","volume":"68","author":"WC Earnshaw","year":"1999","unstructured":"Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem. 1999;68:383\u2013424.","journal-title":"Annu Rev Biochem"},{"key":"3167_CR15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1042\/BJ20041142","volume":"384","author":"P Fuentes-Prior","year":"2004","unstructured":"Fuentes-Prior P, Salvesen GS. The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J. 2004;384:201\u2013232.","journal-title":"Biochem J"},{"key":"3167_CR16","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1111\/j.1572-0241.2004.40573.x","volume":"99","author":"A Feldstein","year":"2004","unstructured":"Feldstein A, Gores GJ. Steatohepatitis and apoptosis: therapeutic implications. Am J Gastroenterol. 2004;99:1718\u20131719.","journal-title":"Am J Gastroenterol"},{"key":"3167_CR17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/hep.21223","volume":"44","author":"A Wieckowska","year":"2006","unstructured":"Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein AE. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology. 2006;44:27\u201333.","journal-title":"Hepatology"},{"key":"3167_CR18","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1002\/hep.26271","volume":"57","author":"M Hatting","year":"2013","unstructured":"Hatting M, Zhao G, Schumacher F, et al. Hepatocyte caspase-8 is an essential modulator of steatohepatitis in rodents. Hepatology. 2013;57:2189\u20132201.","journal-title":"Hepatology"},{"key":"3167_CR19","doi-asserted-by":"crossref","first-page":"e56100","DOI":"10.1371\/journal.pone.0056100","volume":"8","author":"LJ Dixon","year":"2013","unstructured":"Dixon LJ, Flask CA, Papouchado BG, Feldstein AE, Nagy LE. Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis. PLoS One. 2013;8:e56100.","journal-title":"PLoS One"},{"key":"3167_CR20","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1101\/gad.12.6.806","volume":"12","author":"M Woo","year":"1998","unstructured":"Woo M, Hakem R, Soengas MS, et al. Essential contribution of caspase 3\/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 1998;12:806\u2013819.","journal-title":"Genes Dev"},{"key":"3167_CR21","doi-asserted-by":"crossref","unstructured":"Nanji AA. Animal models of nonalcoholic fatty liver disease and steatohepatitis. Clinics in Liver Disease. 2004;8:559\u2013574, ix.","DOI":"10.1016\/j.cld.2004.04.002"},{"key":"3167_CR22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1055\/s-2001-12932","volume":"21","author":"A Koteish","year":"2001","unstructured":"Koteish A, Diehl AM. Animal models of steatosis. Semin Liver Dis. 2001;21:89\u2013104.","journal-title":"Semin Liver Dis"},{"key":"3167_CR23","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","volume":"41","author":"DE Kleiner","year":"2005","unstructured":"Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313\u20131321.","journal-title":"Hepatology"},{"key":"3167_CR24","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1586\/egh.09.32","volume":"3","author":"N Alkhouri","year":"2009","unstructured":"Alkhouri N, Dixon LJ, Feldstein AE. Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev Gastroenterol Hepatol. 2009;3:445\u2013451.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"3167_CR25","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.2741\/1765","volume":"10","author":"AE Feldstein","year":"2005","unstructured":"Feldstein AE, Gores GJ. Apoptosis in alcoholic and nonalcoholic steatohepatitis. Front Biosci. 2005;10:3093\u20133099.","journal-title":"Front Biosci"},{"key":"3167_CR26","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1002\/hep.22183","volume":"47","author":"Z Li","year":"2008","unstructured":"Li Z, Berk M, McIntyre TM, Gores GJ, Feldstein AE. The lysosomal-mitochondrial axis in free fatty acid-induced hepatic lipotoxicity. Hepatology. 2008;47:1495\u20131503.","journal-title":"Hepatology"},{"key":"3167_CR27","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/S0168-8278(03)00460-4","volume":"39","author":"AE Feldstein","year":"2003","unstructured":"Feldstein AE, Canbay A, Guicciardi ME, Higuchi H, Bronk SF, Gores GJ. Diet associated hepatic steatosis sensitizes to Fas mediated liver injury in mice. J Hepatol. 2003;39:978\u2013983.","journal-title":"J Hepatol"},{"key":"3167_CR28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.20283","volume":"40","author":"AE Feldstein","year":"2004","unstructured":"Feldstein AE, Werneburg NW, Canbay A, et al. Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology. 2004;40:185\u2013194.","journal-title":"Hepatology"},{"key":"3167_CR29","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.cell.2005.05.019","volume":"121","author":"DR Green","year":"2005","unstructured":"Green DR. Apoptotic pathways: ten minutes to dead. Cell. 2005;121:671\u2013674.","journal-title":"Cell"},{"key":"3167_CR30","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbpb.2008.05.010","volume":"151","author":"I Chowdhury","year":"2008","unstructured":"Chowdhury I, Tharakan B, Bhat GK. Caspases\u2014an update. Comp Biochem Physiol B Biochem Mol Biol. 2008;151:10\u201327.","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"3167_CR31","doi-asserted-by":"crossref","unstructured":"Barreyro FJ, Holod S, Finocchietto PV et al. The pan-caspase inhibitor emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver Int. 2014. (Epub ahead of print). doi: 10.1111\/liv.12570 .","DOI":"10.1111\/liv.12570"},{"key":"3167_CR32","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/hep.23167","volume":"50","author":"RP Witek","year":"2009","unstructured":"Witek RP, Stone WC, Karaca FG, et al. Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis. Hepatology. 2009;50:1421\u20131430.","journal-title":"Hepatology"},{"key":"3167_CR33","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.jhep.2010.03.016","volume":"53","author":"QM Anstee","year":"2010","unstructured":"Anstee QM, Concas D, Kudo H, et al. Impact of pan-caspase inhibition in animal models of established steatosis and non-alcoholic steatohepatitis. J Hepatol. 2010;53:542\u2013550.","journal-title":"J Hepatol"},{"key":"3167_CR34","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1074\/jbc.M109.074252","volume":"285","author":"N Alkhouri","year":"2010","unstructured":"Alkhouri N, Gornicka A, Berk MP, et al. Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem. 2010;285:3428\u20133438.","journal-title":"J Biol Chem"},{"key":"3167_CR35","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.cld.2009.07.003","volume":"13","author":"WK Syn","year":"2009","unstructured":"Syn WK, Choi SS, Diehl AM. Apoptosis and cytokines in non-alcoholic steatohepatitis. Clin Liver Dis. 2009;13:565\u2013580.","journal-title":"Clin Liver Dis"},{"key":"3167_CR36","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1053\/j.gastro.2004.10.005","volume":"128","author":"M Imamura","year":"2005","unstructured":"Imamura M, Ogawa T, Sasaguri Y, Chayama K, Ueno H. Suppression of macrophage infiltration inhibits activation of hepatic stellate cells and liver fibrogenesis in rats. Gastroenterology. 2005;128:138\u2013146.","journal-title":"Gastroenterology"},{"key":"3167_CR37","first-page":"1858","volume":"119","author":"E Seki","year":"2009","unstructured":"Seki E, De Minicis S, Gwak GY, et al. CCR1 and CCR5 promote hepatic fibrosis in mice. J Clin Investig. 2009;119:1858\u20131870.","journal-title":"J Clin Investig"},{"key":"3167_CR38","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1186\/1755-1536-5-S1-S27","volume":"5","author":"F Tacke","year":"2012","unstructured":"Tacke F. Functional role of intrahepatic monocyte subsets for the progression of liver inflammation and liver fibrosis in vivo. Fibrogenesis Tissue Repair. 2012;5:S27.","journal-title":"Fibrogenesis Tissue Repair"},{"key":"3167_CR39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.22950","volume":"50","author":"KR Karlmark","year":"2009","unstructured":"Karlmark KR, Weiskirchen R, Zimmermann HW, et al. Hepatic recruitment of the inflammatory Gr1\u00a0+\u00a0monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009;50:261\u2013274.","journal-title":"Hepatology"},{"key":"3167_CR40","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/hep.22952","volume":"50","author":"E Seki","year":"2009","unstructured":"Seki E, de Minicis S, Inokuchi S, et al. CCR2 promotes hepatic fibrosis in mice. Hepatology. 2009;50:185\u2013197.","journal-title":"Hepatology"}],"container-title":["Digestive Diseases and Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-014-3167-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10620-014-3167-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-014-3167-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T19:44:15Z","timestamp":1559245455000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10620-014-3167-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,3]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["3167"],"URL":"https:\/\/doi.org\/10.1007\/s10620-014-3167-6","relation":{},"ISSN":["0163-2116","1573-2568"],"issn-type":[{"value":"0163-2116","type":"print"},{"value":"1573-2568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,3]]}}}