Regulation of cardiac fibroblast MMP2 gene expression by scleraxis

Journal of Molecular and Cellular Cardiology
Raghu S NagalingamMichael P Czubryt

Abstract

Remodeling of the cardiac extracellular matrix is responsible for a number of the detrimental effects on heart function that arise secondary to hypertension, diabetes and myocardial infarction. This remodeling consists both of an increase in new matrix protein synthesis, and an increase in the expression of matrix metalloproteinases (MMPs) that degrade existing matrix structures. Previous studies utilizing knockout mice have demonstrated clearly that MMP2 plays a pathogenic role during matrix remodeling, thus it is important to understand the mechanisms that regulate MMP2 gene expression. We have shown that the transcription factor scleraxis is an important inducer of extracellular matrix gene expression in the heart that may also control MMP2 expression. In the present study, we demonstrate that scleraxis directly transactivates the proximal MMP2 gene promoter, resulting in increased histone acetylation, and identify a specific E-box sequence in the promoter to which scleraxis binds. Cardiac myo-fibroblasts isolated from scleraxis knockout mice exhibited dramatically decreased MMP2 expression; however, scleraxis over-expression in knockout cells could rescue this loss. We further show that regulation of MMP2 gene expression by...Continue Reading

Citations

Aug 21, 2019·Journal of Cardiovascular Development and Disease·Michael P Czubryt
Jul 1, 2020·Journal of Experimental & Clinical Cancer Research : CR·Xiaobai LiuYunhui Liu
Jul 28, 2020·International Journal of Molecular Sciences·Miguel Ramírez-AragónCriselda Mendoza-Milla
Nov 6, 2018·Canadian Journal of Physiology and Pharmacology·Ryan WangRushita A Bagchi
Dec 29, 2020·Cellular Signalling·Alexandra M GarvinTaben M Hale

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