Fig. 1.

Gap junctions and transforming growth factor (TGF)-β counterregulate each other. Connexin 43 (Cx43), the major gap junction protein in the myocardium, which is also expressed in renal tubules, may positively regulate TGF-β. The response gene to complement 32 (RGC-32) and SMAD 3, downstream targets of TGF-β, regulate Snail, which is important in the epithelial-mesenchymal transition (EMT) of renal proximal tubule cells. Snail-mediated EMT decreases Cx43 expression, resulting in a negative feedback loop. In some tissues, e.g., kidney, an increase in the Cx43-to-Cx37 ratio could be a regulator of renal fibrosis (27a). Whether this interaction also regulates the expression of TGF-β remains to be determined.