15-Deoxy-Δ12,14-prostaglandin J2 Inhibits Angiotensin II-induced Fibronectin Expression via Hepatocyte Growth Factor Induction in Human Peritoneal Mesothelial Cells
Article first published online: 17 JUL 2009
© 2009 The Authors. Journal compilation © 2009 International Society for Apheresis
Therapeutic Apheresis and Dialysis
Volume 14, Issue 1, pages 43–51, February 2010
How to Cite
Yokoyama, Y., Masaki, T., Kiribayashi, K., Nakashima, A., Kokoroishi, K., Ogawa, T., Kohno, N. and Yorioka, N. (2010), 15-Deoxy-Δ12,14-prostaglandin J2 Inhibits Angiotensin II-induced Fibronectin Expression via Hepatocyte Growth Factor Induction in Human Peritoneal Mesothelial Cells. Therapeutic Apheresis and Dialysis, 14: 43–51. doi: 10.1111/j.1744-9987.2009.00702.x
- Issue published online: 12 FEB 2010
- Article first published online: 17 JUL 2009
- Received June 2008; revised March 2009.
- Hepatocyte growth factor;
- Mesothelial cell;
- Peritoneal fibrosis;
- Proliferator-activated receptor-γ
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an endogenous peroxisome proliferator-activated receptor γ (PPARγ) agonist that suppresses progressive matrix deposition; however, little is known about the effects of 15d-PGJ2 on human peritoneal mesothelial cells (HPMCs). We investigated the following: (i) the expression of PPARγ; (ii) the effect of 15d-PGJ2 on angiotensin II (Ang II)-induced fibronectin (FN) expression and secretion; (iii) the effect of 15d-PGJ2 (with or without Ang II and with or without the specific PPARγ antagonist GW9662) and pioglitazone, a synthetic PPARγ agonist, on hepatocyte growth factor (HGF) expression and secretion; (iv) the effect of HGF on Ang II-induced FN expression and secretion; (v) the expression of c-Met (a specific HGF receptor) and its phospho-signal; and (vi) the involvement of HGF in the effect produced by 15d-PGJ2 using selective c-Met inhibitor PHA-665752. The presence of PPARγ was detected by western blot analysis. 15d-PGJ2 inhibited Ang II-induced FN expression and increased HGF expression, even in the presence of Ang II. This effect of HGF expression was completely prevented by co-treatment with GW9662. Additionally, upregulation of HGF secretion induced by 15d-PGJ2 and HGF production induced by pioglitazone was revealed. We demonstrated the presence of c-Met, and presented evidence that HGF inhibits Ang II-induced FN expression and activates phosphorylation of c-Met, which is blocked by PHA-665752; 15d-PGJ2 also activated c-Met phosphorylation. Furthermore, PHA-665752 attenuates the inhibitory effects of 15d-PGJ2 on FN secretion. These findings suggest that 15d-PGJ2 has a novel and potent antifibrotic effect in HPMC and this action is likely mediated by HGF.