WIF1 causes dysfunction of heart in transgenic mice.
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, cTnT(R141W) and cTnT(R92Q). 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.
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Beijing, People's Republic of China.
Dan
D
Lu
Wei
W
Dong
Xu
X
Zhang
Xiongzhi
X
Quan
Dan
D
Bao
Yingdong
Y
Lu
Lianfeng
L
Zhang
D000199:Actins / Q000096:biosynthesis; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006321:Heart / Q000503:physiopathology*; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D020107:Troponin T / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020107:Troponin T; C118544:Wif1 protein, mouse; D051176:beta Catenin; D020097:Natriuretic Peptide, Brain