Distinct Regulation of B-type Natriuretic Peptide Transcription by p38 MAPK Isoforms

Elina Koivisto (1) , Leena Kaikkonen (1) , Heikki Tokola (1, 2) , Sampsa Pikkarainen (1) , Jani Aro (1) , Harri Pennanen (1) , Teemu Karvonen (1) , Jaana Rysä (1) , Risto Kerkelä (1) , Heikki Ruskoaho (1)

1 Department of Pharmacology and Toxicology
2 Department of Pathology

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 p38β but not p38α increased B-type natriuretic peptide (BNP) mRNA levels as well as atrial natriuretic peptide mRNA levels both and . Overexpression of p38α, in turn, augmented the expression fibrosis-related genes connective tissue growth factor, basic fibroblast growth factor and matrix metalloproteinase-9 both and . p38β-induced BNP transcription was diminished by mutation of GATA-4 binding site, whereas overexpression of MKK6b, an upstream regulator of p38α and p38β, 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.

Mots clés: p38 MAPK; Cardiac hypertrophy; AP-1; GATA-4; BNP; MAP kinases (MAPKs)

Domaines: Biochimie, Biologie Moléculaire

Elina Koivisto, Leena Kaikkonen, Heikki Tokola, Sampsa Pikkarainen, Jani Aro, et al.. Distinct Regulation of B-type Natriuretic Peptide Transcription by p38 MAPK Isoforms. Molecular and Cellular Endocrinology, 2011, ⟨10.1016/j.mce.2011.02.015⟩. ⟨hal-00693834⟩