Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice.

摘要: Reg2/RegIIIbeta is the murine homologue of human secreted HIP/PAP C-type lectin. transgenic mice were protected against acetaminophen-induced acute liver failure and stimulated to regenerate post-hepatectomy. To assess role Reg2, we used Reg2-/- in a model fulminant hepatitis induced by Fas post-hepatectomy regeneration. Within 4 hours J0-2 treatment (0.5 microg/g), only 50% alive but with an increased sensitivity Fas-induced oxidative stress decreased level Bcl-xL. In contrast, resistant Fas, serving as sulfhydryl buffer slow down decreases glutathione mice, regeneration was markedly impaired, 29% mortality delay S-phase activation ERK1/2 AKT. Activation STAT3 began on time at 3 persisted strongly up 72 despite significant accumulation SOCS3. Thus, Reg2 deficiency exaggerated IL-6/STAT-3 mito-inhibition. Because gene activated between 6 24 after hepatectomy wild-type could mediate TNF-alpha/IL-6 priming signaling exerting negative feed-back STAT3/IL-6 allow hepatocytes progress through cell cycle. conclusion, enhanced delayed persistent TNF-alpha/IL6/STAT3 signaling. overexpression promoted resistance accelerated early activation/deactivation STAT3. Reg2/HIP/PAP therefore critical mitogenic antiapoptotic factor for liver.