Abstract
Wnt activity is a key regulator of cardiac progenitor cell self-renewal, differentiation and morphogenesis. However, Wnt inhibitory factor 1 (WIF1), a antagonists of Wnt signaling activity, its potential effects on heart development has not yet been approached by either in vivo or in vitro studies. Here, the expression of WIF1 was regulated in a different way in the dilated and hypertrophic cardiomyopathy heart from transgenic mice by mutations in cardiac troponin T, cTnTR141W and cTnTR92Q. The heart tissue specific transgenic mice of WIF1 was studied using M-mode echocardiography and histologic analyses. Production levels of an array of effectors and transcription factors that impact cellular organization and tissue morphology were measured. The effects of WIF1 on β-catenin pathway could be reversed by LiCl regarding signaling pathways and effector and respondent molecules in H9c2 cells, consistent with the expression levels of c-myc, natriuretic peptide precursor type B and skeletal muscle actin α1. Among the most noteworthy findings were that WIF1 impaired the function and structure of heart, and the effects on β-catenin pathway maybe the course of the former. It is anticipated that our findings will contribute to expansion of our understanding of WIF1 biological function on heart development and possible modes of treatment of heart diseases. Electronic supplementary materialThe online version of this article (doi:10.1007/s11248-013-9738-z) contains supplementary material, which is available to authorized users.
Highlights
Wnt is a key regulator of cardiac progenitor cell selfrenewal, differentiation and morphogenesis (Cohen et al 2008)
The results suggest that Wnt inhibitory factor 1 (WIF1) are involved in the development of the heart and may have contrasting different effects on the pathogenesis of cardiomyopathy
WIF1 is a secreted protein that binds to Wnt proteins and inhibits their activities (Hsieh et al 1999), and it can directly bind to Wnt proteins and inhibit Wnts from binding to their receptors in vertebrates (Hsieh et al 1999)
Summary
Wnt is a key regulator of cardiac progenitor cell selfrenewal, differentiation and morphogenesis (Cohen et al 2008). Various secreted Wnt antagonists interact directly or indirectly to affect Wnt signaling and influence its regulatory processes (Kawano and Kypta 2003), and their modulating capacities are important in cardiac development. Extracellular antagonists of the Wnt signaling pathway include the secreted frizzledrelated protein family, Wnt inhibitory factor 1 (WIF1), and the Cerberus and Dickkopf (Dkk) family. Wnt inhibitory factor 1 was first identified as an expressed sequence tag from human retina with highly conserved among sepecies (Hsieh et al 1999). The WIF1 binds directly to extracellular Wnt ligands, preventing their interaction with the receptors and leading to b-catenin degradation (Hsieh et al 1999). Human WIF1 binds through to eight Wnts [3a,4,5a,7a,9a,11 (Surmann-Schmitt et al 2009), wingless and Xenopus Wnt8] and a protein involved in neuronal differentiation, olfactomedin 1(Nakaya et al 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
