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.