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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/R1856    most recent 00862.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhao, L. Articles by Yamamoto, T. PubMed PubMed Citation Articles by Zhao, L. Articles by Yamamoto, T.

RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

Claudin-6 localized in tight junctions of rat podocytes

¹Department of Structural Pathology, Institute of Nephrology and ²Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences; ³Cooperative Laboratory of Electron Microscopy, Niigata University; and ⁴Institute for Clinical Research, Niigata National Hospital, Niigata, Japan

Submitted 3 December 2007 ; accepted in final form 26 March 2008

Tight junctions rarely exist in podocytes of the normal renal glomerulus, whereas they are the main intercellular junctions of podocytes in nephrosis and in the early stage of development. Claudins have been identified as tight junction-specific integral membrane proteins. Those of podocytes, however, remain to be elucidated. In the present study, we investigated the expression and localization of claudin-6 in the rat kidney, especially in podocytes. Western blot analysis and RT-PCR revealed that the neonatal kidney expressed much higher levels of claudin-6 than the adult kidney. Immunofluorescence microscopy showed intense claudin-6 staining in most of the tubules and glomeruli in neonates. The staining in tubules declined distinctly in adults, whereas staining in glomeruli was well preserved during development. Claudin-6 in glomeruli was distributed along the glomerular capillary wall and colocalized with zonula occludens-1. The staining became conspicuous after kidney perfusion with protamine sulfate (PS) to increase tight junctions in podocytes. Immunoelectron microscopy showed that immunogold particles for claudin-6 were accumulated at close cell-cell contact sites of podocytes in PS-perfused kidneys, whereas a very limited number of immunogold particles were detected, mainly on the basal cell membrane and occasionally at the slit diaphragm and close cell-cell contact sites in normal control kidneys. In puromycin aminonucleoside nephrosis, immunogold particles were also found mainly at cell-contact sites of podocytes. These findings indicate that claudin-6 is a transmembrane protein of tight junctions in podocytes during development and under pathological conditions.

neonate; protamine sulfate; puromycin aminonucleoside