Loss of angiotensin converting enzyme II (ACE2) accelerates the development of liver injury induced by thioacetamide

Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis in renin-angiotensin system (RAS), could play a protective role against liver damages. The purpose of this study is to investigate whether inflammation-mediated liver injury could be affected by ACE2 derived pathways in the RAS. Eight-weeks-old wild-type (WT; C57BL/6) and Ace2 KO (hemizygous Ace2(-ly)) male mice were used to induce liver fibrosis by thioacetamide (TAA) administration (0, 100, and 200 mg/kg BW). The mice administrated with TAA could be successfully induced liver fibrosis in a TAA-dose dependent manner. Compared to WT mice, the results show that Ace2 KO mice have high sensitive, and developed more serious reaction of hepatic inflammation and fibrosis by TAA administration. The physiological and pathological examinations demonstrated higher serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels, infiltration of white blood cells and fibrotic lesions within liver in the Ace2 KO mice. The severe liver damage of Ace2 KO mice were also confirmed by the evidence of higher expression of hepatic inflammation-related genes (IL-6 and Tnf) and fibrosis-related genes (Col1a1, Timp1 and Mmp9). Ace2 gene deficiency could lead to a severe inflammation and collagen remodeling in the liver administrated by TAA, and the responses lead the pathogenesis of liver fibrosis. Our studies provided the main messages and favorable study directions of relationship of Ace2 and liver disease.