Molecular basis of organ fibrosis: Potential therapeutic approaches

Research output: Contribution to journalReview articlepeer-review

97 Scopus citations

Abstract

Fibrosis, a non-physiological wound healing in multiple organs, is associated with end-stage pathological symptoms of a wide variety of vascular injury and inflammation related diseases. In response to chemical, immunological and physical insults, the body's defense system and matrix synthetic machinery respond to healing the wound and maintain tissue homeostasis. However, uncontrolled wound healing leads to scarring or fibrosis, a pathological condition characterized by excessive synthesis and accumulation of extracellular matrix proteins, loss of tissue homeostasis and organ failure. Understanding the actual cause of pathological wound healing and identification of igniter(s) of fibrogenesis would be helpful to design novel therapeutic approaches to control pathological wound healing and to prevent fibrosis related morbidity and mortality. In this article, we review the significance of a few key cytokines (TGF-β, IFN-γ, IL-10) transcriptional activators (Sp1, Egr-1, Smad3), repressors (Smad7, Fli-1, PPAR-γ, p53, Klotho) and epigenetic modulators (acetyltransferase, methyltransferases, deacetylases, microRNAs) involved in major matrix protein collagen synthesis under pathological stage of wound healing, and the potentiality of these regulators as therapeutic targets for fibrosis treatment. The significance of endothelial to mesenchymal transition (EndMT) and senescence, two newly emerged fields in fibrosis research, has also been discussed.

Original languageEnglish (US)
Pages (from-to)461-481
Number of pages21
JournalExperimental Biology and Medicine
Volume238
Issue number5
DOIs
StatePublished - Aug 2013

Keywords

  • ATp300
  • Collagen
  • Egr1
  • EndMT
  • Epigenetics
  • Fibrosis
  • Fli-1
  • HDACi
  • Klotho
  • PPAR-γ
  • Senescence
  • Smad4
  • Smad7
  • Sp1
  • Wound healing
  • microRNA
  • p53

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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