Fig. 8
From: RNA binding protein HuR protects against NAFLD by suppressing long noncoding RNA H19 expression
H19 downregulation alleviates WDSW-induced NAFLD in HuRhKO mice. HuRhKO mice were injected with a recombinant adenovirus encoding an H19 shRNA or control adenovirus (GFP) while being fed ad libitum a WDSW for 4 weeks. a Relative mRNA levels of H19 in livers injected with H19 shRNA adenovirus compared control adenovirus. Data are expressed as the mean ± SEM. Statistical significance relative to control: *p < 0.05, n = 5. b Representative immunoblot images of nuclear SphK2 in the liver are shown. Relative protein levels of nuclear SphK2 were normalized using histone H3. Statistical significance relative to control: *p < 0.05, n = 5. c Representative H&E staining images of the liver sections (scale bar, 20 μm for 40 × magnification). d Representative Picro Sirius Red staining images of the liver sections (scale bar, 20 μm for 40 × magnification). e Schematic diagram of the potential mechanism of HuR in attenuating WDSW-induced NAFLD. The current study demonstrated that HuR functions as an important regulator of hepatic lipid metabolism, enterohepatic bile acid homeostasis, inflammation, and fibrosis by suppressing H19 expression and modulating the SphK2 nuclear protein level. Bile acid-induced activation of S1PR2 may also contribute to NASH fibrosis. Hepatocyte-specific modulation of HuR expression and its downstream target, H19, may be used to develop potential therapeutics for NAFLD