From pathogenesis to therapy--Perspective on treatment strategies in fibrotic diseases

Pharmacol Res. 2015 Oct:100:93-100. doi: 10.1016/j.phrs.2015.06.012. Epub 2015 Jul 16.

Abstract

Although fibrosis is becoming increasingly recognized as a major cause of morbidity and mortality in modern societies, there are very few treatment strategies available that specifically target the pathogenesis of fibrosis. Early in disease, inflammation and vascular changes and an increase in reactive oxygen species play pivotal roles. After inflammation has subsided, fibrosis and scarring are predominant in later phases. Fibrosis is driven by a complex, not-yet fully understood interplay between inflammatory cells on one hand and endothelium and fibroblasts on the other hand. The latter are regarded as the key players due to their extensive synthesis of extracellular matrix components which results in skin and organ fibrosis. Various cytokines orchestrate altered functions of the mentioned cell types. There are promising targets with therapeutic potential that have been extensively characterized in recent years connected with the hope to translate these preclinical results into clinical practice.

Keywords: Fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Endothelium / drug effects
  • Endothelium / metabolism
  • Endothelium / pathology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis / drug therapy*
  • Fibrosis / metabolism
  • Fibrosis / pathology*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology

Substances

  • Cytokines