Administration of glutaredoxin-1 attenuates liver fibrosis caused by aging and non-alcoholic steatohepatitis

Glutaredoxin-1 (Glrx) controls redox signaling and has an anti-apoptotic function. We evaluated the role of Glrx on hepatic cell damage and fibrosis induced by a high-fat diet. We fed mice a high-fat high-fructose diet to induce non-alcoholic steatohepatitis (NASH) and injected AAV-Glrx to express hepatocyte-specific Glrx in diet-induced NASH mice. AAV-Glrx suppressed fibrosis and improved liver function in the NASH liver. We used microarrays to profile gene expression in the NASH liver and find pathways that AAV-Glrx mediated to attenuate fibrosis and NASH progression. 10-week-old C57BL/6J mice were fed a high-fat high-fructose diet to induce non-alcoholic steatohepatitis (NASH). AAV-Cont or AAV-Glrx (1 × 1E12 vg) was administered by intraperitoneal injection after 20 weeks of NASH diet and maintained for another 12 weeks. RNA was isolated from mouse liver (n=5 or 6 each), pooled into three samples per group.