Novel finding of caveolin‐2 in apical membranes of proximal tubule and first detection of caveolin‐2 in urine: A promising biomarker of renal disease

Abstract

Caveolin‐2 (Cav‐2) is expressed in a variety of cell tissue, and it has also been found in renal tissue. The expression of Cav‐2 in proximal tubules is still unclear. The aim of this study was to carry out a complete evaluation of the expression pattern of Cav‐2 in rat renal cortex to clarify and deepen the knowledge about the localization of Cav‐2 in the proximal tubules and also to evaluate its presence in urine. Male Wistar rats were used to assess Cav‐2 expression by Western blot analysis in homogenates, apical, and basolateral membranes from kidney cortex, in lysates and total plasma membranes from renal cortical cell suspensions, in urine, and in urinary exosomes. Cav‐2 was clearly expressed in renal cortex homogenates and in both apical and basolateral membranes isolated from kidney cortex, with a greater expression on the former membranes. It was also observed in lysates and in plasma membranes from cortical cell suspensions. Moreover, Cav‐2 was found in urine and in its exosomal fraction. These results confirmed the presence of Cav‐2 in proximal tubule cells in the kidney of healthy rats, and showed for the first time its expression at the apical membrane of these cells and in urine. Besides, urinary exosomal pathway could be involved in Cav‐2 urinary excretion under normal conditions. We observed an increase in the urinary abundance of Cav‐2 in two models of acute kidney injury, and thus we proposed the urinary excretion of Cav‐2 as a potential biomarker of kidney injury.

Renal Handling of Albumin—From Early Findings to Current Concepts

“…On the other hand, it was demonstrated in these studies, that clathrin-dependent endocytosis is the predominant mechanism of molecules reabsorption [50,51]. Although caveolin expression was detected in the apical membrane of proximal tubular epithelial cells, caveolin dependent endocytosis was never reported [52,53].…”

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

“…Each value represents mean ± standard error from experiments carried out in triplicate on four different tissue‐derived samples or urine‐derived samples for each experimental group. The protein abundances of Oat5 and NGAL in the urine samples were expressed as optical density (O.D., arbitrary units) related to urinary creatinine concentration ([O.D./10 μL]/Cr U ) in order to correct for variations in urine production as previously reported …”

“…For densitometry of immunoblots, samples from treated rats were in order to correct for variations in urine production as previously reported. 10,11,14,46,49…”

Site‐ and structure‐specific characterization of the human urinary N‐glycoproteome with site‐determining and structure‐diagnostic product ions

“…Urine comes from blood yet without homeostasis, which means that urine responds faster to physiological or pathological changes. This feature together with its noninvasive availability has led to urine being increasingly adopted in clinical diagnosis‐related studies including prostatic carcinoma, anti‐tuberculosis therapy, and renal disease 38–42 …”