Caveolin 1 Promotes Renal Water and Salt Reabsorption

Abstract

Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known about their functional role in the kidney. We tested the hypothesis that caveolae modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient (Cav1−/−) mice were studied. Cav1 expression and caveolae formation were present in vascular cells, late distal convoluted tubule and principal connecting tubule and collecting duct cells of WT but not Cav1−/− kidneys. Urinary sodium excretion was increased by 94% and urine flow by 126% in Cav1−/− mice (p < 0.05). A decrease in activating phosphorylation of the Na-Cl cotransporter (NCC) of the distal convoluted tubule was recorded in Cav1−/− compared to WT kidneys (−40%; p < 0.05). Isolated intrarenal arteries from Cav1−/− mice revealed a fourfold reduction in sensitivity to phenylephrine (p < 0.05). A significantly diminished maximal contractile response (−13%; p < 0.05) was suggestive of enhanced nitric oxide (NO) availability. In line with this, the abundance of endothelial NO synthase (eNOS) was increased in Cav1−/− kidneys +213%; p < 0.05) and cultured caveolae-deprived cells showed intracellular accumulation of eNOS, compared to caveolae-intact controls. Our results suggest that renal caveolae help to conserve water and electrolytes via modulation of NCC function and regulation of vascular eNOS.

Aldosterone Rapidly Enhances Levels of the Striatin and Caveolin-1 Proteins in Rat Kidney: The Role of the Mineralocorticoid Receptor

“…Aldosterone-induced oxidation promoting cell defenestration takes place in cav-1-related autophagy [26]. In the kidney, cav-1 promotes renal water and salt reabsorption by modulating sodium-chloride cotransporter function and regulating vascular endothelial nitric oxide [4]. More in vivo studies are needed to elucidate the molecular mechanisms of striatin and cav-1 in modulating aldosterone pathways and, consequently, in regulating kidney function.…”

“…Unfortunately, studies of striatin related to kidney function have not been reported. The cav-1 protein promotes renal water and salt reabsorption via modulation of sodium-chloride cotransporter function and regulation of vascular endothelial nitric oxide [4].…”

The unique structural and functional characteristics of glomerular endothelial cell fenestrations and their potential as a therapeutic target in kidney disease

“…However, both GEnC ( 45 ) and LSEC ( 46 ) fenestrations appear normal in caveolin knockout mice ( 45 ). Caveolin is expressed in GEnCs ( 47 ) but not in fenestrae ( 45 ). Caveolin interacts with mineralocorticoid receptors (MRs), and binding of aldosterone to the caveolin-MR complex induces oxidative signaling cascades ( 48 ).…”

Calcium-Sensing Receptor and Regulation of WNK Kinases in the Kidney

“…Along the same line, caveolae-mediated endocytosis has been implicated in the modulation of TRPV5 surface expression by uromodulin in HEK293 cells [107]. Evaluation of caveolin-1 and caveolae distribution in the mouse and rat kidneys showed their basolateral presence in DCT2 and principal cells (PCs) of CNT/CD but failed to confirm the apical localization of caveolae in vivo [108,109]. Apical caveolin-1 trafficking can be induced by supraphysiological doses of a vasopressin V2 receptor agonist desmopressin, as has been shown in vasopressin-deficient Brattleboro rats [110].…”