Aldosterone-induced cardiomyocyte growth, and fibroblast migration and proliferation are mediated by TRAF3IP2

Naveen K. Somanna, Manjunath Yariswamy, Joseph M. Garagliano, Ulrich Siebenlist, Srinivas Mummidi, Anthony J. Valente, Bysani Chandrasekar

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Sustained activation of the Renin-Angiotensin-Aldosterone System (RAAS) contributes to the pathogenesis of heart failure. Aldosterone (Aldo) is known to induce both myocardial hypertrophy and fibrosis through oxidative stress and proinflammatory pathways. Here we have investigated whether Aldo-mediated cardiomycocyte hypertrophy is dependent on TRAF3IP2, an upstream regulator of IKK and JNK. We also investigated whether the pro-mitogenic and pro-migratory effects of Aldo on cardiac fibroblasts are also mediated by TRAF3IP2. Aldo induced both superoxide and hydrogen peroxide in isolated adult mouse cardiomyocytes (CM), and upregulated TRAF3IP2 expression in part via the mineralocorticoid receptor and oxidative stress. Silencing TRAF3IP2 blunted Aldo-induced IKKβ, p65, JNK, and c-Jun activation, IL-18, IL-6 and CT-1 upregulation, and cardiomyocyte hypertrophy. In isolated adult mouse cardiac fibroblasts (CF), Aldo stimulated TRAF3IP2-dependent IL-18 and IL-6 production, CTGF, collagen I and III expression, MMP2 activation, and proliferation and migration. These in vitro results suggest that TRAF3IP2 may play a causal role in Aldo-induced adverse cardiac remodeling in vivo, and identify TRAF3IP2 as a potential therapeutic target in hypertensive heart disease.

Original languageEnglish (US)
Pages (from-to)1928-1938
Number of pages11
JournalCellular Signalling
Volume27
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Keywords

  • Aldosterone
  • Hypertrophy
  • Migration
  • Mitogenesis
  • RAAS
  • TRAF3IP2

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Somanna, N. K., Yariswamy, M., Garagliano, J. M., Siebenlist, U., Mummidi, S., Valente, A. J., & Chandrasekar, B. (2015). Aldosterone-induced cardiomyocyte growth, and fibroblast migration and proliferation are mediated by TRAF3IP2. Cellular Signalling, 27(10), 1928-1938. https://doi.org/10.1016/j.cellsig.2015.07.001