microRNA-155 Modulates Hepatic Stellate Cell Proliferation, Apoptosis, and Cell Cycle Progression in Rats With Alcoholic Hepatitis via the MAPK Signaling Pathway Through Targeting SOCS1
Authors: Chunhai Gao
Ping Han
Shulan Liu
Dengtao Liu
Wei Gao
Xiaocui Yao
Journal: Frontiers in Pharmacology (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: alcoholic hepatitis; hepatic stellate cell; microRNA-155; mitogen-activated protein kinase signaling pathway; proliferation and apoptosis
Affiliations: Clinical Laboratory, Linyi People's Hospital, Linyi, China., Department of Pulmonary and Critical Care Medicine, Linyi People's Hospital, Linyi, China., Department of Imaging, Linyi People's Hospital, Linyi, China.

Abstract:  The aim of this study was to investigate the regulatory function of the non-coding microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in alcoholic hepatitis (AH) and its potential mechanism associated with the mitogen-activated protein kinase (MAPK) signaling pathway. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TBIL), malondialdehyde (MDA), and superoxide dismutase (SOD) were measured in a rat model of AH. The biological prediction website microRNA.org and dual-luciferase reporter gene assay were used to identify whether SOCS1 was a direct target of miR-155, and the effects of miR-155 and SOCS1 on the viability, cycle progression, and apoptosis of hepatic stellate cells were assessed using RT-qPCR, Western blot assay, MTT assay, Annexin V/PI double staining, and PI single staining. The levels of ALT, AST, MDA, and TBIL and the liver cell morphology were all prominently changed in AH model rats. miR-155 suppressed SOCS1 by specifically binding to SOCS1-3'-UTR to activate the MAPK signaling pathway. SOCS1 had low expression while miR-155 was highly expressed in AH rats. miR-155 promoted hepatic stellate cell viability and cycle progression and reduced cell apoptosis by silencing SOCS1. Together, we find that silenced miR-155 could upregulate SOCS1 and inactivate the MAPK signaling pathway, thereby inhibiting the proliferation of alcoholic hepatic stellate cells and promoting cell apoptosis. 

Retracted: Yes

PubPeer comments:
 Fig 7A.  Cell cycle progression of differently transfected hepatic stellate cells . ![file] These images do not make sense as flow-cytometry results. Were they hand-drawn? , 
 Retracted (not yet dated): https: www.frontiersin.org articles 10.3389 fphar.2021.840009 full ------------------------------------ The journal and Chief Editors retract the 7 April 2020 article cited above. Following publication, concerns were raised regarding the validity of the data in the article. The authors failed to provide the raw data or a satisfactory explanation during the investigation, which was conducted in accordance with Frontiersu2019 policies. Given the concerns, and the lack of raw data, the editors no longer have confidence in the findings presented in the article. This retraction was approved by the Chief Editors of Frontiers in Pharmacology and the Chief Executive Editor of Frontiers. The authors have not responded to any correspondence regarding the retraction. ,