Document Detail


Aldosterone stimulates proliferation of mesangial cells by activating mitogen-activated protein kinase 1/2, cyclin D1, and cyclin A.
MedLine Citation:
PMID:  15975997     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, attention has been focused on the role of aldosterone in the pathophysiology of hypertension and cardiovascular disease. Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. However, the molecular mechanisms of the effects of aldosterone in signal transduction and the cell-cycle progression of mesangial cells are not well known. For determining the signaling pathway of aldosterone in cultured mesangial cells, the effects of aldosterone on the mitogen-activated protein kinase 1/2 (MAPK1/2) pathway and the promoter activities of cyclin D1, cyclin A, and cyclin E were investigated. First, it was shown that the mineralocorticoid receptor (MR) was expressed in rat mesangial cells and glomeruli and that aldosterone stimulated the proliferation of mesangial cells via the MR and MAPK1/2 pathway. Next, it was demonstrated that aldosterone stimulated Ki-RasA, c-Raf kinase, MEK1/2, and MAPK1/2 in rat mesangial cells. Aldosterone induced cyclin D1 and cyclin A promoter activities and protein expressions, as well as the increments of CDK2 and CDK4 kinase activities. The presence of CYP11B2 and 11beta-HSD2 mRNA in rat mesangial cells also was shown. In conclusion, aldosterone seems to exert mainly MR-induced effects that stimulate c-Raf, MEK1/2, MAPK1/2, the activities of CDK2 and CDK4, and the cell-cycle progression in mesangial cells. MR antagonists may serve as a potential therapeutic approach to mesangial proliferative disease.
Authors:
Yoshio Terada; Takahiko Kobayashi; Hitoshi Kuwana; Hiroyuki Tanaka; Seiji Inoshita; Michio Kuwahara; Sei Sasaki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-06-23
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  16     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-21     Completed Date:  2006-02-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2296-305     Citation Subset:  IM    
Affiliation:
Department of Nephrology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. yterada.kid@tmd.ac.jp
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
Aldosterone / metabolism,  pharmacology*
Aldosterone Synthase / metabolism
Animals
Blotting, Western
Cell Cycle
Cell Proliferation
Cyclin A / genetics,  metabolism*
Cyclin D1 / genetics,  metabolism*
Cyclin E / genetics
Disease Progression
Flow Cytometry
Genes, Reporter
Kidney / cytology,  injuries,  pathology
Kidney Cortex / metabolism
Kidney Glomerulus / metabolism
Luciferases / metabolism
MAP Kinase Signaling System
Male
Mesangial Cells / metabolism*,  pathology
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Promoter Regions, Genetic
Proto-Oncogene Proteins / chemistry
Proto-Oncogene Proteins c-raf / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Mineralocorticoid / biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Thymidine / metabolism
Time Factors
Transfection
ras Proteins
Chemical
Reg. No./Substance:
0/Cyclin A; 0/Cyclin E; 0/KRAS protein, human; 0/Proto-Oncogene Proteins; 0/Receptors, Mineralocorticoid; 136601-57-5/Cyclin D1; 50-89-5/Thymidine; 52-39-1/Aldosterone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2; EC 1.13.12.-/Luciferases; EC 1.14.15.4/Aldosterone Synthase; EC 2.7.11.1/Proto-Oncogene Proteins c-raf; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.6.5.2/ras Proteins

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