Peroxisome proliferator-activated receptor gamma 1 (PPAR gamma 1) expresses in rat mesangial cells and PPAR gamma agonists modulate its differentiation

Thiazolidinediones, synthetic ligands of peroxisome proliferator-activated receptor gamma (PPAR gamma), 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 PPAR gamma activation of kidney cells, and we examined the expression of PPAR gamma and the effect of PPAR gamma agonists, troglitazone and 15-de oxy-delta-prostaglandin J2 (15d-PGJ2), on the proliferation and differentia tion in rat mesangial cells. A single band of mRNA of PPAR gamma with a pre dicted size was detected in reverse transcription-polymerase chain reaction products (RT-PCR) using established PCR probes of PPAR gamma. PPAR gamma p rotein in rat mesangial cells was identified as PPAR gamma 1 by a Western b lot. In a gel mobility shift assay to determine a binding activity of PPAR gamma, the nuclear protein from rat mesangial cells bound to a P-32-labeled oligonucleotide probe, including PPAR response elements. A synthetic and a natural ligand of PPAR gamma, troglitazone and 15d-PGJ2, decreased thymidi ne incorporation in a dose dependent manner. After 7 days incubation with t roglitazone and 15d-PGJ2, alpha-smooth muscle actin expression, a marker of mesangial cell de-differentiation, was decreased significantly compared to that of control. These results indicate that PPAR gamma 1 is expressing in rat mesangial cells, and PPAR gamma 1 activation with its agonists modulat es the proliferation and differentiation of cultured rat mesangial cells. ( C) 2000 Elsevier Science B.V. All rights reserved.