Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis

Biomolecules. 2021 Jul 23;11(8):1095. doi: 10.3390/biom11081095.

Abstract

Myofibroblasts are contractile, α-smooth muscle actin-positive cells with multiple roles in pathophysiological processes. Myofibroblasts mediate wound contractions, but their persistent presence in tissues is central to driving fibrosis, making them attractive cell targets for the development of therapeutic treatments. However, due to shared cellular markers with several other phenotypes, the specific targeting of myofibroblasts has long presented a scientific and clinical challenge. In recent years, myofibroblasts have drawn much attention among scientific research communities from multiple disciplines and specialisations. As further research uncovers the characterisations of myofibroblast formation, function, and regulation, the realisation of novel interventional routes for myofibroblasts within pathologies has emerged. The research community is approaching the means to finally target these cells, to prevent fibrosis, accelerate scarless wound healing, and attenuate associated disease-processes in clinical settings. This comprehensive review article describes the myofibroblast cell phenotype, their origins, and their diverse physiological and pathological functionality. Special attention has been given to mechanisms and molecular pathways governing myofibroblast differentiation, and updates in molecular interventions.

Keywords: anti-scarring therapy; fibrosis; myofibroblast; transforming growth factor-β1; wound healing.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cicatrix
  • ErbB Receptors / metabolism
  • Fibrosis / therapy*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / metabolism
  • Ligands
  • Mice
  • Myofibroblasts / metabolism*
  • Phenotype
  • Signal Transduction / physiology
  • Skin / pathology*
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Wnt Proteins / metabolism
  • Wound Healing
  • beta Catenin / metabolism

Substances

  • Actins
  • CD44 protein, human
  • Hyaluronan Receptors
  • Ligands
  • Smad Proteins
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • Wnt Proteins
  • beta Catenin
  • Hyaluronic Acid
  • ErbB Receptors