An integrative view of serpins in health and disease: the contribution of SerpinA3

Am J Physiol Cell Physiol. 2021 Jan 1;320(1):C106-C118. doi: 10.1152/ajpcell.00366.2020. Epub 2020 Oct 28.

Abstract

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular diseases, and kidney disorders are intensively studied to find effective therapeutic targets. Given the serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin has been associated with diverse pathophysiological events. In particular, we focus here on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.

Keywords: angiogenesis; inflammation; physiopathology; serine protease inhibitors; suicide substrate inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Chronic Disease*
  • Fibrosis
  • Health*
  • Humans
  • Inflammation / metabolism
  • Neovascularization, Physiologic
  • Oxidative Stress
  • Serpins / metabolism*
  • Signal Transduction

Substances

  • SERPINA3 protein, human
  • Serpins