Connexins and the kidney

Abstract

Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules, there is morphological evidence for the presence of gap junction plaques only in the proximal tubules. In the distal nephron, Cx30, Cx30.3, and Cx37 are expressed, but it is not known whether they form gap junctions connecting neighboring cells or whether they primarily act as hemichannels. As in other systems, the major function of Cxs in the kidney appears to be intercellular communication, although they may also form hemichannels that allow cellular secretion of large signaling molecules. Renal Cxs facilitate vascular conduction, juxtaglomerular apparatus calcium signaling, and tubular purinergic signaling. Accordingly, current evidence points to roles for these Cxs in several important regulatory mechanisms in the kidney, including the renin angiotensin system, tubuloglomerular feedback, and salt and water reabsorption. At the systemic level, renal Cxs may help regulate blood pressure and may be involved in hypertension and diabetes.

Effect of Novel Gasotransmitter hydrogen sulfide on renal fibrosis and connexins expression in diabetic rats

“…Exogenous H 2 S can protect against diabetes-induced hypertrophyand myocardialfibrosis, dysfunction, oxidative stress,apoptosis. 16,17 The pathological change of renal fibrosis exists in the whole course of the occurrence and development of DN; its manifestations include increase of collagenous fiber elements of extracellular matrix in mesangial cells, increase of collagen in renal tubule basement membrane and increase of renal tubule interstitial collagen and fibronection secretion. Collagen II is an important component of ECM.…”

TGFβ modulates cell-to-cell communication in early epithelial-to-mesenchymal transition

“…While the presence of GJs in the kidney has long been known, details on their function in the proximal tubule are sparse. Studies on renal vasculature have confirmed a role for various connexins in renin secretion and the regulation of blood pressure [31], but minimal data exist on their role in tubular function, where levels are also high. The novel findings presented here demonstrate a link between high glucose, TGF-β1, impaired cell adhesion and reduced GJ abundance in the proximal tubule.…”

High Bone Mass in Mice Lacking Cx37 Because of Defective Osteoclast Differentiation

“…Cx37 is expressed in monocytes/macrophages, platelets, kidney, and ovaries, but it is more abundant in endothelial cells in the blood vessels (7)(8)(9). However, Cx37 deletion does not impair vascular function because Cx40, which is also expressed in endothelial cells, can compensate for the absence of Cx37 (10,11).…”