N-cadherin is depleted from proximal tubules in experimental and human acute kidney injury

Abstract

Ischemia remains the most common cause of acute kidney injury (AKI). Decreased intercellular adhesion and alterations in adhesion molecules may contribute to the loss of renal function observed in AKI. In the present study, we evaluated the distribution of adhesion molecules in the human kidney and analyzed their expression in human and experimental AKI. Specimens of human kidneys obtained from patients with and without AKI were stained for the cell adhesion molecules E-cadherin, N-cadherin and beta-catenin. Experimental AKI in rats was induced by renal artery clamping. Immunostaining and immunoblotting were carried out for E-cadherin, N-cadherin and beta-catenin. Proximal tubule cells from opossum kidneys (OKs) were used to analyze the effect of chemical hypoxia (ATP depletion) in vitro. In the adult human kidney, N-cadherin was expressed in proximal tubules, while E-cadherin was expressed in other nephron segments. beta-Catenin was expressed in both proximal and distal tubules. In human AKI and in ischemic rat kidneys, N-cadherin immunostaining was depleted from proximal tubules. There was no change in E-cadherin or beta-catenin. In vitro, OK cells expressed N-cadherin only in the presence of collagen, and ATP depletion led to a depletion of N-cadherin. Collagen IV staining was reduced in ischemic rat kidneys compared to controls. The results of the study suggest that N-cadherin may play a significant role in human and experimental AKI.

Urinary Biomarkers in Obstructive Nephropathy

“…This may be explained by the fact that L1CAM is a membrane glycoprotein normally expressed at the basolateral membrane of the collecting-duct epithelial cell, which with injury is translocated to the apical membrane (23,24). We studied other potentially important biomarkers, including AQP2, a water channel (25); E-cadherin, a cell adhesion molecule (8,9,26,27); and N-cadherin, another member of the cadherin family (9,28,29). Although the excretion of these candidate proteins was altered in our casepatients, they did not correlate with renal function or with a reduced GFR.…”

Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model

“…AKI induced by ischaemia or toxins was characterised by the impairment of kidney function due to the loss of tubular epithelial polarity 31 . Tissue integrity was checked by the immunohistochemical detection of the adhesion junction molecules E- and N-cadherin.…”

“…In humans, AKI induced by ischaemia or calcineurin inhibitors depleted the expression of N-cadherin while E-cadherin was unaffected 31 . Our study corroborated these findings and demonstrated that the depletion of N-cadherin was attenuated by pBM-MSCs.…”

Genetic or Pharmacologic Blockade of EGFR Inhibits Renal Fibrosis

“…[25][26][27] As shown in Supplemental Figure 2, many tubules were labeled by FITC-PNA from cortex through medulla, but only tubules in the cortex were costained with EGFR. Because the majority of renal tubules in the cortex are proximal tubules, this finding suggests that EGFR is predominantly expressed in proximal tubular cells.…”