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Open AccessArticle

The Functional Role of Zinc Finger E Box-Binding Homeobox 2 (Zeb2) in Promoting Cardiac Fibroblast Activation

1
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E0J9, Canada
2
Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E0J9, Canada
3
Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H2A6, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 3207; https://doi.org/10.3390/ijms19103207
Received: 5 September 2018 / Revised: 28 September 2018 / Accepted: 5 October 2018 / Published: 17 October 2018
(This article belongs to the Special Issue Nutrition and Cardiovascular Health)
Following cardiac injury, fibroblasts are activated and are termed as myofibroblasts, and these cells are key players in extracellular matrix (ECM) remodeling and fibrosis, itself a primary contributor to heart failure. Nutraceuticals have been shown to blunt cardiac fibrosis in both in-vitro and in-vivo studies. However, nutraceuticals have had conflicting results in clinical trials, and there are no effective therapies currently available to specifically target cardiac fibrosis. We have previously shown that expression of the zinc finger E box-binding homeobox 2 (Zeb2) transcription factor increases as fibroblasts are activated. We now show that Zeb2 plays a critical role in fibroblast activation. Zeb2 overexpression in primary rat cardiac fibroblasts is associated with significantly increased expression of embryonic smooth muscle myosin heavy chain (SMemb), ED-A fibronectin and α-smooth muscle actin (α-SMA). We found that Zeb2 was highly expressed in activated myofibroblast nuclei but not in the nuclei of inactive fibroblasts. Moreover, ectopic Zeb2 expression in myofibroblasts resulted in a significantly less migratory phenotype with elevated contractility, which are characteristics of mature myofibroblasts. Knockdown of Zeb2 with siRNA in primary myofibroblasts did not alter the expression of myofibroblast markers, which may indicate that Zeb2 is functionally redundant with other profibrotic transcription factors. These findings add to our understanding of the contribution of Zeb2 to the mechanisms controlling cardiac fibroblast activation. View Full-Text
Keywords: Zeb2; cardiac fibroblast; activated myofibroblast; cardiac fibrosis; fibroblast contractility Zeb2; cardiac fibroblast; activated myofibroblast; cardiac fibrosis; fibroblast contractility
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Jahan, F.; Landry, N.M.; Rattan, S.G.; Dixon, I.M.C.; Wigle, J.T. The Functional Role of Zinc Finger E Box-Binding Homeobox 2 (Zeb2) in Promoting Cardiac Fibroblast Activation. Int. J. Mol. Sci. 2018, 19, 3207.

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