Distinct regulation of B-type natriuretic peptide transcription by p38 MAPK isoforms.
Mol Cell Endocrinol
; 338(1-2): 18-27, 2011 May 16.
Article
em En
| MEDLINE
| ID: mdl-21354263
ABSTRACT
Persistent controversy underlies the functional roles of specific p38 MAPK isoforms in cardiac biology and regulation of hypertrophy-associated genes. Here we show that adenoviral gene transfer of p38ß but not p38α increased B-type natriuretic peptide (BNP) mRNA levels in vitro as well as atrial natriuretic peptide mRNA levels both in vitro and in vivo. Overexpression of p38α, in turn, augmented the expression fibrosis-related genes connective tissue growth factor, basic fibroblast growth factor and matrix metalloproteinase-9 both in vitro and in vivo. p38ß-induced BNP transcription was diminished by mutation of GATA-4 binding site, whereas overexpression of MKK6b, an upstream regulator of p38α and p38ß, activated BNP transcription through both GATA-4 and AP-1. Overexpression of MKK3, upstream regulator of p38α, induced BNP transcription independently from AP-1 and GATA-4. These data provide new evidence for diversity in downstream targets and functional roles of p38 pathway kinases in regulation of hypertrophy-associated cardiac genes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Peptídeo Natriurético Encefálico
/
Proteínas Quinases p38 Ativadas por Mitógeno
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Endocrinol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Finlândia