Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Cells, Cultured
-
Cyclopentanes / chemistry*
-
Dose-Response Relationship, Drug
-
Enzyme Activation
-
Enzyme Inhibitors / pharmacology
-
Flavonoids / pharmacology
-
Glomerular Mesangium / enzymology*
-
Humans
-
Hypoglycemic Agents / pharmacology
-
Immunologic Factors / pharmacology
-
JNK Mitogen-Activated Protein Kinases
-
Ligands
-
MAP Kinase Signaling System*
-
Mitogen-Activated Protein Kinases / metabolism
-
Phosphatidylinositol 3-Kinases / metabolism
-
Prostaglandin D2 / analogs & derivatives
-
Prostaglandin D2 / pharmacology
-
Prostaglandins / pharmacology*
-
Receptors, Cytoplasmic and Nuclear / metabolism
-
Thiazoles / pharmacology
-
Thiazolidinediones*
-
Transcription Factors / metabolism
Substances
-
15-deoxy-delta(12,14)-prostaglandin J2
-
Cyclopentanes
-
Enzyme Inhibitors
-
Flavonoids
-
Hypoglycemic Agents
-
Immunologic Factors
-
Ligands
-
Prostaglandins
-
Receptors, Cytoplasmic and Nuclear
-
Thiazoles
-
Thiazolidinediones
-
Transcription Factors
-
Phosphatidylinositol 3-Kinases
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinases
-
cyclopentenone
-
Prostaglandin D2
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
-
ciglitazone