PMID: 26807171Jan 26, 2016Paper

TNF receptor-associated factor 6 (TRAF6) mediates the angiotensin-induced non-canonical TGF-β pathway activation of c-kit(+) cardiac stem cells

American Journal of Translational Research
Qing CaoShuyan Chen

Abstract

Cardiac stem cells (CSCs) can differentiate into cardiac muscle-like cells upon stimulation by angiotensin II (Ang II). TNF receptor-associated factor 6 (TRAF6) has been shown to promote JNK- and p38-induced myogenic differentiation and mediate Smad-independent activation of TGF-β. However, the detailed mechanisms underlying the activation of these signaling pathways are not entirely known. Herein, we hypothesized that Ang II could promote the differentiation of CSCs into cardiac muscle-like cells by non-canonical TGF-β/TRAF6 signaling pathway, and sought to test the hypothesis. C-kit(+) CSCs were isolated from neonatal Sprague Dawley (SD) rats, and their c-kit status was confirmed with immunofluorescence staining. A TGF-β type I receptor inhibitor (SB431542) was used to inhibit SMAD2/3 phosphorylation. The small interfering RNA (siRNA)-mediated knockdown of TRAF6 was used to investigate the role of TRAF6 in TGF-β signaling. Rescue of TRAF6 siRNA transfected cells with a 3'UTR-deleted siRNA insensitive construct was performed to rule out any off-target effects of the siRNA. TRAF6 dominant-negative (TRAF6DN) vector was constructed and used to infect c-kit(+) CSCs. Our results showed that the increase in JNK and p38 activation by...Continue Reading

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