Analyses of hepatocellular proliferation in a mouse model of α-1-antitrypsin deficiency

• DOI: 10.1002/hep.20118
• Publication Date: 2004-03-26T08:02:40Z
• Authors: David A. Rudnick; Yunjun Liao; Jae-Koo An; Louis J. Muglia; David H. Perlmutter; Jeffrey H. Teckman
• Keywords: Alpha 1-antitrypsin deficiency

α-1-Antitrypsin (α1-AT) deficiency is the most common cause of metabolic pediatric liver disease. Hepatocellular injury caused by toxicity mutant α-1-antitrypsin Z (α1-ATZ) molecule retained within hepatocytes. In these studies, we used PiZ transgenic mouse model α1-AT to examine hepatocellular proliferation in response chronic resulting from this The results showed increased and caspase 9 activation male mice compared with female wild-type mice. Hepatic mRNA protein expression also were mice, suggesting that greater males hepatotoxicity associated intracellular α1-ATZ accumulation. Testosterone treatment a level comparable males. hepatocytes devoid globules had proliferative advantage globule-containing However, relative because both globule-devoid exhibited after partial hepatectomy. conclusion, data indicate retention regenerative stimulus leading proliferation, gender-specific signals influence degree hepatic injury, have over cells accumulate protein. This selective suggests transplantation may be applicable for other slowly progressive diseases (Hepatology 2004;39:1048-1055.)