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15‐Deoxy‐Δ 12,14 ‐prostaglandin J 2 Inhibits Angiotensin II‐induced Fibronectin Expression via Hepatocyte Growth Factor Induction in Human Peritoneal Mesothelial Cells
Author(s) -
Yokoyama Yukio,
Masaki Takao,
Kiribayashi Kei,
Nakashima Ayumu,
Kokoroishi Keiko,
Ogawa Takahiko,
Kohno Nobuoki,
Yorioka Noriaki
Publication year - 2010
Publication title -
therapeutic apheresis and dialysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 53
eISSN - 1744-9987
pISSN - 1744-9979
DOI - 10.1111/j.1744-9987.2009.00702.x
Subject(s) - hepatocyte growth factor , endocrinology , medicine , angiotensin ii , peroxisome proliferator activated receptor , receptor , agonist , mesothelium , fibronectin , secretion , prostaglandin , biology , microbiology and biotechnology , peritoneum , extracellular matrix , pathology
15‐Deoxy‐Δ 12,14 ‐prostaglandin J 2 (15d‐PGJ 2 ) is an endogenous peroxisome proliferator‐activated receptor γ (PPARγ) agonist that suppresses progressive matrix deposition; however, little is known about the effects of 15d‐PGJ 2 on human peritoneal mesothelial cells (HPMCs). We investigated the following: (i) the expression of PPARγ; (ii) the effect of 15d‐PGJ 2 on angiotensin II (Ang II)‐induced fibronectin (FN) expression and secretion; (iii) the effect of 15d‐PGJ 2 (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‐PGJ 2 using selective c‐Met inhibitor PHA‐665752. The presence of PPARγ was detected by western blot analysis. 15d‐PGJ 2 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‐PGJ 2 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‐PGJ 2 also activated c‐Met phosphorylation. Furthermore, PHA‐665752 attenuates the inhibitory effects of 15d‐PGJ 2 on FN secretion. These findings suggest that 15d‐PGJ 2 has a novel and potent antifibrotic effect in HPMC and this action is likely mediated by HGF.