Clinical Aspects of Connexins 37, 40, 43, 45 Expression in the Embryonic and Adult Kidneys

Abstract

Nowdays, there is a wide variety of judgments regarding the specific expression of some forms of connexins (Cx) in the renin apparatus of the embryonic and adult kidneys. Establishing the exact intrarenal localization of Cx 40, 37, 43, 45 is a prerequisite for understanding their functional role in normal renal organogenesis, as well as in maintaining fluid homeostasis and controlling renin secretion. At 8–10 weeks of embryonic development, the expression of various Cx is observed in the epithelium of blood vessels and renal tubules, as well as in the region of the renal renin apparatus, but with different patterns of expression and intensity over time. During embryogenesis, the expression of Cx 40 is higher than that of Cx 43, 37, and 45. In the postnatal period, the expression of Cx 40 decreases, while the expression of others increases. Cx 40 is involved in the formation of the renin apparatus in the developing kidney, while Cx 37, Cx 43, and Cx 45 are involved in signaling important for postnatal maintenance of kidney function and blood pressure control. Knockout Cx 45 is a lethal mutation that leads to impaired differentiation of smooth muscle tissue of arterioles. On the contrary, the deletion of individual genes Cx 37, 40 and 43 has little effect on renal organogenesis, probably due to the redundancy and interchangeability of various connexin isoforms. Experimental studies in the adult kidney demonstrate that arterial endothelial cells express Cx 40 and Cx 37 and, to a lesser extent, Cx 43, while smooth muscle cells express Cx 45. The cells of the renin apparatus are characterized by the expression of Cx 37, Cx 40, Cx 43 and Cx 45, with the highest content of Cx 40, especially in juxtaglomerular cells. Adequate and coordinated work of Cx is crucial for the regulation of renal hemodynamics and renin secretion in nephrology. The use of specific connexin-mimetic peptides may lead to the development of more effective methods for controlling renin secretion.