Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)
STAT5b is a key effector of NRG-1/ERBB4-mediated myocardial growth
Julkaisun tekijät: Vaparanta Katri, Jokilammi Anne, Paatero Ilkka, Merilahti Johannes A, Heliste Juho, Hemanthakumar Karthik Amudhala, Kivelä Riikka, Alitalo Kari, Taimen Pekka, Elenius Klaus
Kustantaja: EMBO Press
Julkaisuvuosi: 2023
Journal: EMBO Reports
Tietokannassa oleva lehden nimi: EMBO reports
Lehden akronyymi: EMBO Rep
ISSN: 1469-221X
eISSN: 1469-3178
DOI: http://dx.doi.org/10.15252/embr.202256689
Verkko-osoite: https://doi.org/10.15252/embr.202256689
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/179321707
The growth factor Neuregulin-1 (NRG-1) regulates myocardial growth and is currently under clinical investigation as a treatment for heart failure. Here, we demonstrate in several in vitro and in vivo models that STAT5b mediates NRG-1/EBBB4-stimulated cardiomyocyte growth. Genetic and chemical disruption of the NRG-1/ERBB4 pathway reduces STAT5b activation and transcription of STAT5b target genes Igf1, Myc, and Cdkn1a in murine cardiomyocytes. Loss of Stat5b also ablates NRG-1-induced cardiomyocyte hypertrophy. Dynamin-2 is shown to control the cell surface localization of ERBB4 and chemical inhibition of Dynamin-2 downregulates STAT5b activation and cardiomyocyte hypertrophy. In zebrafish embryos, Stat5 is activated during NRG-1-induced hyperplastic myocardial growth, and chemical inhibition of the Nrg-1/Erbb4 pathway or Dynamin-2 leads to loss of myocardial growth and Stat5 activation. Moreover, CRISPR/Cas9-mediated knockdown of stat5b results in reduced myocardial growth and cardiac function. Finally, the NRG-1/ERBB4/STAT5b signaling pathway is differentially regulated at mRNA and protein levels in the myocardium of patients with pathological cardiac hypertrophy as compared to control human subjects, consistent with a role of the NRG-1/ERBB4/STAT5b pathway in myocardial growth.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
