Renal ischemia–reperfusion injury causes intercalated cell-specific disruption of occludin in the collecting duct

Department of Anatomy, Ewha Womans University School of Medicine, 911-1 Mok-6-dong, Yangcheon-ku, Seoul 158-710, Korea.
Histochemie (Impact Factor: 2.93). 11/2011; 136(6):637-47. DOI: 10.1007/s00418-011-0881-4
Source: PubMed

ABSTRACT Renal ischemic events open tight junctions and disrupt epithelial polarity. The purpose of this study was to examine the effects of ischemia-reperfusion (IR) injury on expression and distribution of the tight junction proteins, occludin and ZO-1, in the rat kidney. IR injury was induced by clamping both renal pedicles for 30 min and animals were killed at 6 h after the reperfusion. IR injury decreased blood bicarbonate level, but did not persistently alter pH, Na(+), K(+), or Cl(-). In control kidneys, occludin immunoreactivity was intense in the tight junctions in the thick ascending limb, distal convoluted tubule, and collecting duct, moderate in the thin limbs of the loop of Henle, and was not detected in the proximal tubule, glomerulus, and blood vessels. ZO-1 was expressed in the same sites in which occludin was expressed, and additionally was also expressed in the proximal tubule, glomerulus, and vascular endothelial cells. IR kidneys exhibited damaged renal tubular epithelial cells in both proximal tubule and collecting duct segments in the outer medulla. In the collecting duct, the response of intercalated cells and principal cells differed. Following IR injury, intercalated cells, but not principal cells, lost their normal epithelial polarity and were frequently extruded into the tubule lumen. Occludin, instead of being localized to tight junctions, was localized diffusely in the cytoplasm in intercalated cells of IR kidneys. Principal cells, in contrast, were not detectably affected and neither occludin nor ZO-1 expression were altered in response to IR injury. The normal localization of ZO-1 expression to tight junction sites in both the proximal tubule and collecting duct was altered in response to IR, and, instead, ZO-1 expression was present diffusely in the cytoplasm. IR injury did not alter detectably either occludin or ZO-1 localization to the tight junction of the thick ascending limb cells. The abundance of total occludin protein by immunoblot analysis was not changed with IR injury. These results demonstrate that renal IR injury causes tight junction disruptions in both the proximal tubule and the collecting duct, and that altered distribution of the tight junction protein, occludin, may play a critical role in the collecting duct dysfunction which IR induces.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Systemic inflammation is known to target tubular epithelial cells (TECs), leading to acute kidney injury. Tubular cells have been implicated in the response to inflammatory mediators in ischaemic and septic renal damage. Moreover, loss of tubular cells by apoptosis or epithelial-to-mesenchymal transition may ingenerate conditions that lead to progression towards chronic kidney disease. On the other hand, TECs may actively contribute to the production of inflammatory mediators that may propagate the injury locally or in distant organs. In the present review, we discuss the tubular cell response and its contribution to systemic inflammation.
    Nephrology Dialysis Transplantation 03/2014; 29(11). DOI:10.1093/ndt/gfu046 · 3.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coordinated cell proliferation and ability to form intercellular seals are essential features of epithelial tissue function. Tight junctions (TJs) classically act as paracellular diffusion barriers. More recently, their role in regulating epithelial cell proliferation in conjunction with scaffolding zonula occludens (ZO) proteins has come to light. The kidney collecting duct (CD) is a model of tight epithelium that displays intense proliferation during embryogenesis followed by very low cell turnover in the adult kidney. Here, we examined the influence of each ZO protein (ZO-1, -2 and -3) on CD cell proliferation. We show that all 3 ZO proteins are strongly expressed in native CD and are present at both intercellular junctions and nuclei of cultured CD principal cells (mCCDcl1). Suppression of either ZO-1 or ZO-2 resulted in increased G0/G1 retention in mCCDcl1 cells. ZO-2 suppression decreased cyclin D1 abundance while ZO-1 suppression was accompanied by increased nuclear p21 localization, the depletion of which restored cell cycle progression. Contrary to ZO-1 and ZO-2, ZO-3 expression at intercellular junctions dramatically increased with cell density and relied on the presence of ZO-1. ZO-3 depletion did not affect cell cycle progression but increased cell detachment. This latter event partly relied on increased nuclear cyclin D1 abundance and was associated with altered β1-integrin subcellular distribution and decreased occludin expression at intercellular junctions. These data reveal diverging, but interconnected, roles for each ZO protein in mCCDcl1 proliferation. While ZO-1 and ZO-2 participate in cell cycle progression, ZO-3 is an important component of cell adhesion.
    Cell cycle (Georgetown, Tex.) 10/2014; 13(19):3059-3075. DOI:10.4161/15384101.2014.949091 · 5.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: E-cadherin is a cell adhesion molecule that plays an important role in maintaining renal epithelial polarity and integrity. The purpose of this study was to determine the exact cellular localization of E-cadherin in the pig kidney. Kidney tissues from pigs were processed for light and electron microscopy immunocytochemistry, and immunoblot analysis. The same size bands were detected by immunoblot in rat and pig kidneys. In the pig kidney, strong E-cadherin expression was observed in the basolateral plasma membrane domain of the tubular epithelial cells. E-cadherin immunolabeling was not detected in glomeruli and blood vessels in the pig kidney. Double-labeling identified that E-cadherin was expressed in the calbindin D28k-positive distal convoluted tubule and H(+)-ATPase-positive collecting duct, but not in the aquaporin 1-positive, N-cadherin-positive proximal tubule. Interestingly, in contrast to the rat, E-cadherin immunoreactivity was not expressed at detectable levels in the Tamm-Horsfall protein-positive thick ascending limb in the pig kidney. Immunoelectron microscopy confirmed that E-cadherin was localized at both the lateral membranes and the basal infoldings of the collecting duct. These results suggest that E-cadherin may be a critical adhesion molecule in the distal convoluted tubule and collecting duct cells in the pig kidney.
    Journal of veterinary science (Suwŏn-si, Korea) 07/2013; 14(4). DOI:10.4142/jvs.2013.14.4.381 · 1.14 Impact Factor

Preview (2 Sources)

Available from