A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma.
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-delta(12,14)-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 PPARgamma is shown to be expressed by mesangial cells, the thiazolidinedione PPARgamma agonist ciglitazone does not activate ERK. Additionally, a synthetic PPARgamma 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 PPARgamma.
Wilmer
W A
WA
Department of Internal Medicine, Ohio State University School of Medicine and Public Health, Columbus, Ohio 43210, USA.
Dixon
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C
Lu
L
L
Hilbelink
T
T
Rovin
B H
BH
D002478:Cells, Cultured; D003517:Cyclopentanes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000201:enzymology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008024:Ligands; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D008024:Ligands; D011453:Prostaglandins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C013905:cyclopentenone; D015230:Prostaglandin D2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C039671:ciglitazone