MiR‐19a Affects Hepatocyte Autophagy via Regulating lncRNA NBR2 and AMPK/PPARα in D‐GalN/Lipopolysaccharide‐Stimulated Hepatocytes. Issue 1 (24th July 2017)

• Record Type: Journal Article
• Authors: Liu, Yan‐Min; Ma, Jin‐Hui; Zeng, Qing‐Lei; Lv, Jun; Xie, Xu‐Hua; Pan, Ya‐Jie; Yu, Zu‐Jiang
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 1(2018)
• Page Start: 358
• Page End: 365
• Publication Date: 2017-07-24
• Subjects: ACUTE LIVER FAILURE -- AMPK/PPARα -- AUTOPHAGY -- miR‐19a -- NBR2; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26188
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: This study aims to evaluate the potential involvement and regulatory mechanism of miR‐19a in hepatocytes autophagy of acute liver failure (ALF). The in vitro hepatocytes injury model of primary hepatocyte and hepatocytes line HL‐7702 was established by D‐galactosamine (D‐GalN) and lipopolysaccharide (LPS) co‐treatment. Relative expression level of miR‐19a and NBR2 was determined by qRT‐PCR. Protein expression of AMPK/PPARα and autophagy‐related gene was determined by Western blot. In hepatic tissue of 20 ALF patients and D‐GalN/LPS‐stimulated hepatocytes, miR‐19a was upregulated and NBR2 was downregulated. D‐GalN/LPS stimulation caused the inactivation of AMPK/PPARα signaling and the decrease of autophagy‐related LC3‐II/LC3‐I ratio and beclin‐1 expression in hepatocytes. The expression of both AMPK/PPARα and NBR2 were negatively controlled by miR‐19a overexpression or knockdown. Moreover, both NBR2 and PPARα were targeted regulated by miR‐19a according to luciferase reporter assay. In D‐GalN/LPS‐stimulated hepatocytes, AMPK activation promoted PPARα expression. AMPK inactivation inhibited the pro‐autophagy effect of miR‐19a and caused the decrease of LC3‐II/LC3‐I ratio and beclin‐1 expression. PPARα activation abrogated the anti‐autophagy effect of miR‐19a mimic and caused the increase of LC3‐II/LC3‐I ratio and beclin‐1 expression. NBR2 knockdown reversed the anti‐autophagy impact of miR‐19a inhibitor and caused the decrease of LC3‐II/LC3‐I ratio and beclin‐1 expression. In summary, our data suggested that miR‐19a negatively controlled the autophagy of hepatocytes attenuated in D‐GalN/LPS‐stimulated hepatocytes via regulating NBR2 and AMPK/PPARα signaling. J. Cell. Biochem. 119: 358–365, 2018. © 2017 Wiley Periodicals, Inc. Abstract : Our data suggested that miR‐19a negatively controlled autophagy of hepatocytes attenuated in D‐GalN/LPS‐stimulated hepatocytes via targeted regulating NRB2 and AMPK/PPARα signaling.