High-Level Connexin Expression in the Human Juxtaglomerular Apparatus

Recent evidence obtained in rodents indicates that gap junctions in the juxtaglomerular apparatus play an important role in the control of renin-producing cells and in tubuloglomerular signaling. These gap junctions are formed by cell-specific expression patterns of the vascular connexins Cx37, Cx40, Cx43 and Cx45. In order to obtain a first indication if gap junctions might play a similar important functional role in the juxtaglomerular apparatus of human kidneys, this study aimed to characterize the juxtaglomerular localization of Cx40, Cx37, Cx43 and Cx45 in human kidney specimens. We found Cx37, Cx40 and Cx43, but not Cx45 expression in high density in the extraglomerular mesangium. Renin-producing cells displayed strong immunoreactivity for Cx40 and Cx37. Cx37, Cx40 and Cx43 were also seen in the endothelium of arteries/arterioles outside of the glomeruli, whereas Cx45 was located in vascular smooth muscle cells. All four connexins were also expressed within the glomeruli. These findings indicate that the expression pattern of vascular connexins in the human kidney cortex is very similar to that previously found for mouse and rat kidneys, suggesting that the intrarenal expression pattern of vascular connexins is conserved among the mammalian species. Because of this similarity, and in particular in view of the strong expression of Cx37 and Cx40 in the juxtaglomerular area, we infer that those functions of connexins that have already been demonstrated for rodent kidneys, such as a central role of Cx40 for the development and function of renin-producing cells and for tubuloglomerular signal transmission, might hold for human kidneys as well.