Glycogen synthase kinase-3β: a promising candidate in the fight against fibrosis

Theranostics. 2020 Sep 23;10(25):11737-11753. doi: 10.7150/thno.47717. eCollection 2020.

Abstract

Fibrosis exists in almost all organs/tissues of the human body, plays an important role in the occurrence and development of diseases and is also a hallmark of the aging process. However, there is no effective prevention or therapeutic method for fibrogenesis. As a serine/threonine (Ser/Thr)-protein kinase, glycogen synthase kinase-3β (GSK-3β) is a vital signaling mediator that participates in a variety of biological events and can inhibit extracellular matrix (ECM) accumulation and the epithelial-mesenchymal transition (EMT) process, thereby exerting its protective role against the fibrosis of various organs/tissues, including the heart, lung, liver, and kidney. Moreover, we further present the upstream regulators and downstream effectors of the GSK-3β pathway during fibrosis and comprehensively summarize the roles of GSK-3β in the regulation of fibrosis and provide several potential targets for research. Collectively, the information reviewed here highlights recent advances vital for experimental research and clinical development, illuminating the possibility of GSK-3β as a novel therapeutic target for the management of tissue fibrosis in the future.

Keywords: Aging; Epithelial-mesenchymal transition; Fibrosis; Glycogen synthase kinase-3β; Signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / pathology
  • Animals
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / drug effects
  • Fibrosis / drug therapy
  • Fibrosis / pathology*
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Kidney / pathology
  • Liver / pathology
  • Lung / pathology
  • Mice
  • Myocardium / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3 beta