Beraprost sodium, an analogue of prostacyclin, induces the expression of mitogen-activated protein kinase phosphatase and inhibits the proliferation of cultured mesangial cells.
Beraprost sodium, an analogue of prostacyclin, increases intracellular cyclic adenosine monophosphate (cAMP) in cultured glomerular mesangial cells. We examined the effect of beraprost on mesangial cell proliferation. Beraprost was able to inhibit fetal bovine serum-stimulated proliferation of mesangial cells in concentrations enough to increase cellular cAMP. By northern blot analysis, beraprost induced the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in a dose- and time-dependent manner, similarly to dibutyryl cAMP and adrenomedullin. These results indicate that beraprost inhibits the proliferation of mesangial cells and one of the mechanisms might be cAMP-dependent induction of MKP-1.
Togawa
M
M
Third Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
Haneda
M
M
Araki
S
S
Sugimoto
T
T
Isono
M
M
Hidaka
H
H
Yasuda
H
H
Kashiwagi
A
A
Kikkawa
R
R
D000818:Animals; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D054638:Dual Specificity Phosphatase 1; D004790:Enzyme Induction; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000201:enzymology; D006131:Growth Inhibitors / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D008297:Male; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018797:Cell Cycle Proteins; D006131:Growth Inhibitors; D017874:Immediate-Early Proteins; C048081:beraprost; D011464:Epoprostenol; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases