Peroxisome proliferator-activated receptor γ1 (PPARγ1) expresses in rat mesangial cells and PPARγ agonists modulate its differentiation

Abstract

Thiazolidinediones, synthetic ligands of peroxisome proliferator-activated receptor γ (PPARγ), are reported to have direct beneficial effects on diabetic nephropathy without lowering blood glucose levels in human and rat. We hypothesized these effects of thiazolidinediones might be derived from PPARγ activation of kidney cells, and we examined the expression of PPARγ and the effect of PPARγ agonists, troglitazone and 15-deoxy-δ-prostaglandin J2 (15d-PGJ2), on the proliferation and differentiation in rat mesangial cells. A single band of mRNA of PPARγ with a predicted size was detected in reverse transcription-polymerase chain reaction products (RT-PCR) using established PCR probes of PPARγ. PPARγ protein in rat mesangial cells was identified as PPARγ1 by a Western blot. In a gel mobility shift assay to determine a binding activity of PPARγ, the nuclear protein from rat mesangial cells bound to a 32P-labeled oligonucleotide probe, including PPAR response elements. A synthetic and a natural ligand of PPARγ, troglitazone and 15d-PGJ2, decreased thymidine incorporation in a dose dependent manner. After 7 days incubation with troglitazone and 15d-PGJ2, α-smooth muscle actin expression, a marker of mesangial cell de-differentiation, was decreased significantly compared to that of control. These results indicate that PPARγ1 is expressing in rat mesangial cells, and PPARγ1 activation with its agonists modulates the proliferation and differentiation of cultured rat mesangial cells.