AdipoRs- a potential therapeutic target for fibrotic disorders

Expert Opin Ther Targets. 2019 Feb;23(2):93-106. doi: 10.1080/14728222.2019.1559823. Epub 2018 Dec 20.

Abstract

Introduction: Fibrotic disorders are a leading cause of morbidity and mortality; hence effective treatments are still vigorously sought. AdipoRs (AdipoR1 and Adipo2) are responsible for the antifibrotic effects of adiponectin (APN). APN exerts antifibrotic effects by binding to its receptors. APN concentration and AdipoR expression are closely associated with fibrotic disorders. Decreased AdipoR expression may reduce APN-AdipoR signaling, while the upregulation of AdipoR expression may restore the anti-fibrotic effects of APN. Loss of APN signaling exacerbates fibrosis in vivo and in vitro. Areas covered: We assess the relationship between APN and fibrotic disorders, the structure of receptors for APN and the pathways accounting for APN or its analogs blocking fibrotic disorders. This article also discusses designed APN products and their therapeutic prospects for fibrotic disorders. Expert opinion: AdipoRs have a critical role in blocking fibrosis. The development of small-molecule agonists toward this target represents a valid drug development pathway.

Keywords: AMPK and PPAR-α signaling pathway; APN-AdipoR-dependent signal transduction; AdipoR; anti-fibrotic effects; systemic and organ-specific fibrosis disorders.

Publication types

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

MeSH terms

  • Adiponectin / metabolism*
  • Animals
  • Drug Development / methods*
  • Fibrosis / drug therapy*
  • Fibrosis / pathology
  • Humans
  • Receptors, Adiponectin / agonists
  • Signal Transduction

Substances

  • ADIPOQ protein, human
  • ADIPOR1 protein, human
  • ADIPOR2 protein, human
  • Adiponectin
  • Receptors, Adiponectin