The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis

J Dermatol Sci. 2010 Sep;59(3):153-62. doi: 10.1016/j.jdermsci.2010.06.008. Epub 2010 Jul 3.


Systemic sclerosis (SSc) is an autoimmune inflammatory disease with unknown etiology characterized by microvascular injury and fibrosis of the skin and internal organs. A growing body of evidence suggests that deficiency of the transcription factor Fli1 (Friend leukemia integration-1) has a pivotal role in the pathogenesis of SSc. Fli1 is expressed in fibroblasts, endothelial cells, and immune cells, and has important roles in the activation, differentiation, development, and survival of these cells. Previous studies demonstrated that Fli1 is downregulated in SSc fibroblasts by an epigenetic mechanism and a series of experiments with Fli1-deficient animal models revealed that Fli1 deficiency in fibroblasts and endothelial cells reproduces the histopathologic features of fibrosis and vasculopathy in SSc, respectively. In this article, we review the impact of Fli1 deficiency on the pathogenesis of SSc and discuss a new therapeutic strategy for SSc by targeting the transcription factor Fli1.

Publication types

  • Review

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Autoimmune Diseases / drug therapy
  • B-Lymphocytes / drug effects
  • Benzamides
  • Collagen Type I / antagonists & inhibitors
  • Down-Regulation
  • Drug Therapy, Combination
  • Epigenesis, Genetic
  • Extracellular Matrix / drug effects
  • Fibroblasts / drug effects
  • Gene Expression / drug effects
  • Hematopoiesis / drug effects
  • Humans
  • Imatinib Mesylate
  • Macrolides / pharmacology
  • Mice
  • Phosphorylation / drug effects
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Protein c-fli-1 / genetics
  • Proto-Oncogene Protein c-fli-1 / metabolism*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / enzymology*
  • Scleroderma, Systemic / pathology
  • Scleroderma, Systemic / physiopathology
  • T-Lymphocytes / drug effects


  • Benzamides
  • Collagen Type I
  • FLI1 protein, human
  • Macrolides
  • Piperazines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Protein c-fli-1
  • Pyrimidines
  • Imatinib Mesylate