A Cyclopentenone Prostaglandin Activates Mesangial MAP Kinase Independently of PPARγ

• Published in: Biochemical and biophysical research communications 2001-02, Vol.281 (1), p.57-62
• Main Authors: Wilmer, William A., Dixon, Cynthia, Lu, Ling, Hilbelink, T., Rovin, Brad H.
• Format: Article
• Language: English
• Subjects: cyclopentenone prostaglandin; extracellular signal-regulated kinase; glomerulus; mesangial cell; mitogen-activated protein kinase; phosphatidylinositol-3 kinase; PPAR; thiazolidinedione
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.4301

The mitogen-activated protein (MAP) kinases mediate the response of renal glomerular mesangial cells to a variety of physiologic and pathologic stimuli. This investigation examines the effect of the cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) on MAP kinases in human mesangial cells. We show that 15d-PGJ2 dose-dependently increases the extracellular signal-regulated kinase (ERK) activity of human mesangial cells, but has no effect on Jun-NH2-terminal kinase or p38 MAP kinase. Despite the fact that 15d-PGJ2 is a peroxisome proliferator-activated receptor (PPAR) ligand, and PPARγ is shown to be expressed by mesangial cells, the thiazolidinedione PPARγ agonist ciglitazone does not activate ERK. Additionally, a synthetic PPARγ antagonist does not attenuate the activation of ERK by 15d-PGJ2. 15d-PGJ2-mediated ERK activation is however blocked by the MEK inhibitor PD 098059, appears to require phosphatidylinositol-3 kinase, but is independent of protein kinase C activation. These results demonstrate a novel effect of 15d-PGJ2 to induce ERK in human mesangial cells independently of PPARγ.