MC (mesangial cell) proliferation is closely linked to the progression of glomerular disease. It has been reported that cAMP effectors suppress MC proliferation, inhibiting activation of MAPK (mitogen-activated protein kinase). In fibroblasts, activation of MAPK induces the expression of type D cyclin, whereas, in MCs, this induction has not been shown. In the present study, we explored the effects of cAMP on MAPK and expression of cell-cycle-regulated proteins. PDGF (platelet-derived growth factor) stimulated MAPK activity, up-regulated protein levels of cyclin D1, CDK2 (cyclin-dependent kinase 2) and PCNA (proliferating cell nuclear antigen), decreased the protein level of p27 and increased DNA synthesis. Fsk (forskolin) or PD98059 suppressed PDGF-induced DNA synthesis. Both agents inhibited PDGF-stimulated mRNA and protein expression of cyclin D1 and CDK2. Fsk or PD98059 also inhibited protein expression of PCNA and blocked a decrease in p27 protein. Fsk induced the phosphorylation of Raf-1 at Ser259, which was inhibited by KT5720. These data suggest that cAMP inhibits MC proliferation through inhibition of MAPK activity, and this mechanism partly involves alteration in the levels of cell-cycle-regulated proteins.
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July 2004
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Research Article|
June 23 2004
Role of cyclins in cAMP inhibition of glomerular mesangial cell proliferation
Chiharu ITO;
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
Correspondence: Dr Chiharu Ito (e-mail [email protected]).
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Hisashi YAMAMOTO;
Hisashi YAMAMOTO
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Yusuke FURUKAWA;
Yusuke FURUKAWA
†Division of Molecular Hematopoiesis, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Shin-ichi TAKEDA;
Shin-ichi TAKEDA
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Tetsu AKIMOTO;
Tetsu AKIMOTO
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Osamu IIMURA;
Osamu IIMURA
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Yasuhiro ANDO;
Yasuhiro ANDO
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Yasushi ASANO;
Yasushi ASANO
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Eiji KUSANO
Eiji KUSANO
*Division of Nephrology, Department of Internal Medicine, Jichi Medical School, Tochigi, Japan
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Publisher: Portland Press Ltd
Received:
October 13 2003
Revision Received:
February 23 2004
Accepted:
March 02 2004
Accepted Manuscript online:
March 02 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2004
Clin Sci (Lond) (2004) 107 (1): 81–87.
Article history
Received:
October 13 2003
Revision Received:
February 23 2004
Accepted:
March 02 2004
Accepted Manuscript online:
March 02 2004
Citation
Chiharu ITO, Hisashi YAMAMOTO, Yusuke FURUKAWA, Shin-ichi TAKEDA, Tetsu AKIMOTO, Osamu IIMURA, Yasuhiro ANDO, Yasushi ASANO, Eiji KUSANO; Role of cyclins in cAMP inhibition of glomerular mesangial cell proliferation. Clin Sci (Lond) 1 July 2004; 107 (1): 81–87. doi: https://doi.org/10.1042/CS20030335
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