LAUSR

Objective Glutaredoxin-1 (Glrx) is a cytosolic enzyme which removes glutathione (GSH) adducts of protein thiols (S-glutathionylation), and controls protein functions including cellular signaling and gene transcription. We previously showed that Glrx knockout middle-aged mice developed liver steatosis and Glrx replenishment by viral gene transfer suppressed lipid accumulation in the liver (Shao 2016). It is reported that decreasing GSH adducts by inhibiting glutathione-S-transferase attenuates bleomycin-induced lung fibrosis in mice. Therefore, we determine whether up-regulated Glrx can attenuate age-induced liver fibrosis and functional changes. Methods Global Glrx transgenic (TG) and wild type (WT) mice of age 9-28 months were used to obtain liver sections to assess fibrotic areas by Picrosirius red collagen staining. Gene expression was assessed in the liver by RNA extraction and RT-qPCR. Hepatocytes and hepatic stellate cells were isolated to examine the effects of in vitro Glrx overexpression on collagen synthesis. Results Our data showed that collagen staining in the liver significantly increased in WT aged mice (> 18 months old) compared to WT middle-aged mice (9 months). Overexpression of Glrx in aged TG mice attenuated collagen deposition compared to WT aged mice. TGFβ mRNA expression in the liver was lower in TG than WT mice. Conclusion Data indicate that aging increases liver fibrosis and Glrx overexpression suppresses the fibrotic change, in part, by inhibiting TGFβ expression. Further studies are required to examine signaling pathways and Glrx target(s) in aging liver. This study may demonstrate the protective role of Glrx and its anti-fibrotic effects in the liver.