Peroxisome proliferator-activated receptor γ agonists reduce cell proliferation and viability and increase apoptosis in systemic sclerosis fibroblasts

Br J Dermatol. 2013 Jan;168(1):129-35. doi: 10.1111/j.1365-2133.2012.11199.x. Epub 2012 Oct 5.

Abstract

Background: No study has evaluated the effect of the peroxisome proliferator-activated receptor γ (PPARγ) agonists on cell viability, proliferation and apoptosis in cultured systemic sclerosis (SSc) fibroblasts.

Objectives: The effects of two pure PPARγ agonists (rosiglitazone and pioglitazone) in cultured SSc fibroblasts were evaluated and compared with effects in normal fibroblasts.

Methods: The study included evaluation of cell viability and proliferation (based on the cleavage of tetrazolium salts and measurement of absorbance of the cell proliferation reagent WST-1), and determination of cell apoptosis (by means of the Hoechst dye uptake).

Results: Rosiglitazone or pioglitazone (20μmolL(-1) ) significantly reduced cell proliferation (cell count of 75% and 83% compared with baseline, respectively, after 2h) and cell viability (absorbance reductions of 25% and 22% compared with baseline, respectively, after 2 h), and increased apoptosis (apoptotic cell percentages 9·9% and 8·6%, respectively, after 48h of incubation) in SSc fibroblasts, whereas they did not present a significant influence on control fibroblasts.

Conclusions: The effects of rosiglitazone or pioglitazone shown on SSc fibroblasts raise the hypothesis of a therapeutic role for PPARγ agonists in patients affected by SSc.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Humans
  • Male
  • Middle Aged
  • PPAR gamma / agonists*
  • Pioglitazone
  • Rosiglitazone
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / pathology
  • Thiazolidinediones / pharmacology*

Substances

  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Pioglitazone