Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts

SummaryPeroxisome proliferator-activated receptor-γ (PPAR-γ) agonists are increasingly used in patients with diabetes, and some studies have suggested a beneficial effect on organ fibrosis, but their effects on dermal cell growth and extracellular matrix (ECM) turnover are unknown. To investigate the effect of the PPAR-γ agonist troglitazone on cell growth and matrix production in human dermal fibroblasts (HDF), HDF were cultured and grown in a different concentration of troglitazone. PPAR-γ expression and matrix production were measured in HDF in the presence of troglitazone. The mRNA expressions of TGF-β1, collagen I (Col I) and fibronectin (FN) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein of transforming growth factor-β1 (TGF-β1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of Col I and FN were determined by Western blotting. The mRNA expression of TGF-β1, Col I and FN were significantly decreased in HDF in 15–30 μmol l−1 troglitazone compared to the control group with Dulbecco's modified Eagle's medium (P < 0.01). An obvious decrease of TGF-β1 protein was found in troglitazone-treated groups as compared to the control group (P < 0.05). Exposure of HDF to troglitazone reduced col I secretion (P < 0.05), and fibronectin secretion (P < 0.05). This study suggests that PPAR-γ agonist will provide a novel approach with therapeutic potential in dermal fibrosis, such as hypertrophic scar, keloid and so on.