Regulation of Runx2 and Other Downstream Factors in the TGFβ Pathway in Cardiac Epithelial to Mesenchymal Transition and Disease

Abstract

Epithelial-mesenchymal transition (EMT) transforms developing embryonic endothelial cells of the heart into mesenchymal cells in the process of activation of downstream regulators of the TGFβ pathway, a major component in EMT signaling, such as the positive transcription factor, Runx2. EMT has been shown to occur in pathogenic, cardiac diseases in the adult as well as in developmental embryonic situations. Here, we explore the Runx2 isoforms and their role in each of these processes, as well as the roles of Runx2’s inhibition on downstream transcription and intracellular (stem-cell possessing) factors, Zeb2 and ALDH1, respectively. We concluded that Runx2 isoforms show a relationship in the calcification of the heart, and that Runx2-I expression is also in the embryonic stages. Also, TGFβ-2 induces Runx2 expression, while silencing RNA against Runx2 reduces its prominence, and essentially induces expression of Zeb2 and ALDH1 through a limited regulation. By deciphering the roles of these fundamental yet intricate players and mechanisms in EMT, a gateway to deciphering potential target therapeutics will also be prominent in future developments for patients with congenital cardiac disease.