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Spironolactone increases integrin beta3 gene expression in kidney and heart muscle cells.

Abstract：

:In clinical trials of heart failure, spironolactone, an antagonist of the mineralocorticoid receptor (MR), reduced mortality rates by unknown mechanisms. We hypothesized that spironolactone functions by upregulating expression of certain cardiovascular genes. An RNA differential display technique was used to identify genes whose expression was increased by spironolactone in an Xenopus kidney epithelial cell line (A6), a known target of aldosterone. We found that integrin beta3 gene expression was increased by spironolactone, and reversed by aldosterone or dexamethasone in a dose dependent manner. Competition binding studies and RT-PCR indicate the presence of MR in A6 cells, suggesting that regulation of expression occurred primarily through MR. Spironolactone also increased integrin beta3 expression in rat neonatal cardiomyocytes. In summary, spironolactone increases integrin beta3 gene expression in kidney epithelial cells and cardiomyocytes. The findings suggest new mechanisms for spironolactone actions with possible relevance to treatment of heart disease.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Chun TY,Bloem L,Pratt JH

doi

10.1016/s0303-7207(02)00112-0

keywords:

subject

Has Abstract

pub_date

2002-08-30 00:00:00

pages

175-82

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303720702001120

journal_volume

194

pub_type

杂志文章

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