Silencing of GDF11 suppresses hepatocyte apoptosis to relieve LPS/D‐GalN acute liver failure

Abstract

AbstractIn this paper, we generated a short hairpin RNA growth differentiation factor‐11 (sh‐GDF11) and evaluated the effects of sh‐GDF11 on the pathogenesis of acute liver failure (ALF) in vitro and in vivo. Through bioinformatics study, the key gene related to ALF was assayed. Lipopolysaccharide (LPS) and D‐galactoamine (D‐GalN) were applied to establish the mouse model of LPS/D‐GalN‐induced liver injury, and TNF‐α and D‐Gal were used to construct an in vitro cell model, followed by treatment of sh‐GDF11 for analysis of liver cell proliferation. Bioinformatics analysis showed that the protective effect of sh‐GDF11 on ALF may be mediated by phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. The results of in vitro study found that sh‐GDF11 could promote cell proliferation and inhibit death by blocking the PI3K/Akt/mTOR signaling pathway. In vivo animal experiments further confirmed that sh‐GDF11 could suppress hepatocyte apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway. sh‐GDF11 relieved LPS/D‐GalN‐induced ALF by blocking the PI3K/Akt/mTOR signaling pathway, emphasizing its critical role in LPS/D‐GalN‐induced ALF treatment.