Acta Biochim Biophys Sin (Shanghai). 2022 Sep 25;54(9):1257-1267.doi: 10.3724/abbs.2022119.

本文采用的英格恩产品: 增强型ECL发光液

The activation of M 3 muscarinic receptor reverses liver injuryvia the Sp1/lncRNA Gm2199/miR-212 axis

Affiliations

Affiliations

  • 1 Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Pharmaceutical, Hainan Medical University, Haikou 571199, China.
  • 2 Institute of Traditional Chinese Medicine, Hainan Medical University, Haikou 571199, China.
  • 3 Department of Pharmacology, Harbin Medical University, Harbin 150081, China.
  • 4 Hainan Medical University First Affiliated Hospital of Department of Anesthesiology, Haikou 570102, China.

Free PMC article

Abstract

Muscarinic acetylcholine receptors (MRs) play important roles in the regulation of hepatic fibrosis and the receptor agonists and antagonists can affect hepatocyte proliferation. However, little is known about the impact of M 3R subtypes and associated signaling pathways on liver injury. The aim of this study is to explore the function and mechanism of M 3R in the regulation of liver injury. We evaluate liver injury and detect the changes in related indexes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), and transforming growth factor-β1 (TGF-β1), after administration of an M 3R agonist. Western blot analysis and qRT-PCR show that the transcription factor Sp1 and long noncoding RNA (lncRNA) Gm2199 are also changed significantly. Rescue assay is performed to further confirm that M 3R contributes to the progression of hepatocyte proliferation through regulating Sp1 and Gm2199. The activated M 3R can specifically regulate Gm2199 by inhibiting the expression of Sp1. Meanwhile, Gm2199 directly regulates miR-212, and ERK is a potential target of miR-212. Collectively, these findings define a novel mechanism for activating M 3R to reverse liver injury, which affects hepatocyte proliferation through the Sp1/Gm 2199/miR-212/ERK axis.

Keywords: M muscarinic acetylcholine receptor (M R); liver injury; lncRNA Gm2199; miR-212; transcription factor Sp1.

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