Relaxin Family Peptide Receptor 1 Activation Stimulates Peroxisome Proliferator-Activated Receptor Gamma
Relaxin (RLX) has antifibrotic effects in a number of tissues. Many of these effects are similar to those induced by the activators of peroxisome proliferator-activated receptor gamma (PPAR?), raising the possibility that a mechanism for RLX's antifibrotic effects may involve activation of the PPAR? pathway. This study investigated the effect of RLX on PPARs and their mechanism of upregulation. It shows that RLX stimulates ligand-independent PPAR activation in a dose-dependent manner. The combined effect of RLX and PPAR? agonists was superadditive, suggesting that both agents might be used together for an increased antifibrotic effect. RLX caused increased expression of the PPAR? target genes CD36 and LXR?. RLX's effect was mimicked by forskolin and partially blocked by pertussis toxin, suggesting that RLX works through a cAMP/protein kinase A pathway to activate PPAR?. A better understanding of this pathway might help in the amelioration of fibrotic diseases.
peroxisome proliferator-activated receptor (ppar) relaxin-3 (rlx-3) insulin-like peptides (insl3) peroxisome proliferator response element (ppre) relaxin family peptide receptor1 (rxfp1)