Transcriptional regulation of endothelial-to-mesenchymal transition in cardiac fibrosis: role of myocardin-related transcription factor A and activating transcription factor 31

• Published in: Canadian journal of physiology and pharmacology Vol. 95; no. 10; pp. 1263 - 1270
• Main Authors: Sharma, Vibhuti, Dogra, Nilambra, Saikia, Uma Nahar, Khullar, Madhu
• Format: Journal Article
• Language: English
• Published: NRC Research Press 2017
• Subjects: ATF-3; cardiac fibrosis; diabetes; diabète; EndMT; fibrose cardiaque; MRTF-A; TEndM
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2016-0634

The etiology of cardiac fibrogenesis is quite diverse, but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined. Myocardin-related transcription factor A facilitates the transcription of cytoskeletal genes by serum response factor during fibrosis; therefore, its specific role in cardiac EndMT might be of importance. Activation of activating transcription factor 3 (ATF-3) during cardiac EndMT is speculative, since ATF-3 responds to a transforming growth factor β (TGF-β) stimulus and controls the expression of the primary epithelial-to-mesenchymal transition markers Snail, Slug, and Twist. Although the role of TGF-β in EndMT-mediated cardiac fibrosis has been established, targeting of the TGF-β ligand has not proven to be a viable anti-fibrotic strategy owing to the broad functional importance of this ligand. Thus, targeting of downstream transcriptional mediators may be a useful therapeutic approach in attenuating cardiac fibrosis. Here, we discuss some of the transcription factors that may regulate EndMT-mediated cardiac fibrosis and their involvement in type 2 diabetes.