Integrins as a drug target in liver fibrosis

Liver Int. 2022 Mar;42(3):507-521. doi: 10.1111/liv.15157. Epub 2022 Jan 28.

Abstract

As the worldwide prevalence of chronic liver diseases is high and continuing to increase, there is an urgent need for treatment to prevent cirrhosis-related morbidity and mortality. Integrins are heterodimeric cell-surface proteins that are promising targets for therapeutic intervention. αv integrins are central in the development of fibrosis as they activate latent TGFβ, a known profibrogenic cytokine. The αv subunit can form heterodimers with β1, β3, β5, β6 or β8 subunits and one or more of these integrins are central to the development of liver fibrosis, however, their relative importance is not understood. This review summarises the current knowledge of αv integrins and their respective β subunits in different organs, with a focus on liver fibrosis and the emerging preclinical and clinical data with regards to αv integrin inhibitors.

Keywords: fibrosis; integrins; liver cirrhosis; liver disease; non-alcoholic steatohepatitis.

Publication types

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

MeSH terms

  • Humans
  • Integrin alphaV / metabolism
  • Integrins* / metabolism
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / metabolism
  • Pharmaceutical Preparations*
  • Transforming Growth Factor beta / metabolism

Substances

  • Integrin alphaV
  • Integrins
  • Pharmaceutical Preparations
  • Transforming Growth Factor beta