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      Different Type and Localization of CD44 on Surface Membrane of Regenerative Renal Tubular Epithelial Cells in vivo

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          Background: CD44 is a transmembrane glycoprotein comprising an extracellular domain, a transmembrane domain, and a cytoplasmic tail. Previous studies demonstrated that CD44 was generally restricted to lateral-basal plasma membrane (PM) of epithelial cells, whether it localized on apical PM in vivo has not been clarified. Methods: In this study, we used a gentamicin-induced acute tubular necrosis (ATN) and spontaneous recovery model in rats and two distinct antibodies, an anti-rat distal extracellular domain (OX49) of standard CD44 (CD44-OX49) and an anti-rat CD44 cytoplasmic tail (CD44CPT), to survey the localization of CD44-OX49 and CD44CPT on the PM in renal tubular epithelial cells in different recovery stages after ATN with immunohistochemistry and immunoelectron-microscopic examinations. Results: CD44-OX49 was localized not only on the lateral-basal PM in tubular epithelial cells, but also on the apical surface membrane in PCNA-positive newly regenerative tubular epithelial cells in early recovery stages after ATN. However, CD44CPT was only localized on the lateral-basal PM. The immunoelectron-microscopic results showed that CD44-OX49 localization was changed from the apical to lateral to basal surface membrane in renal tubular epithelial cells during the recovery process after ATN, finally disappearing from basal PM when normal polarized epithelial cells formed. Conclusions: These results suggest that there were two types of CD44 including CD44 without a cytoplasmic tail localizing on the apical surface membrane related to newly regenerative epithelial cells, and CD44 with a cytoplasmic tail localizing on the lateral-basal PM related to establishment of tubular epithelial cell polarity after ATN in vivo.

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          Most cited references 9

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          Origins of cell polarity.

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            Mechanisms of cell polarity: sorting and transport in epithelial cells.

            The recent discovery of widely distributed targeting determinants, which govern the polarized cell-surface distribution of plasma membrane proteins in epithelial cells, has significantly changed our view of how polarized cells generate functionally distinct membrane domains. Together with the surprising finding that the same determinants are recognized on both the biosynthetic and the endocytic pathways, it now appears likely that a common epigenetic code may exist that controls molecular sorting of membrane proteins in a wide variety of polarized, and perhaps even non-polarized, cell types.
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              Expression, roles, receptors, and regulation of osteopontin in the kidney.

              Osteopontin (OPN) is a secreted glycoprotein in both phosphorylated and non-phosphorylated forms. It contains an Arg-Gly-Asp cell-binding sequence and a thrombin-cleavage site. OPN is mainly present in the loop of Henle and distal nephrons in normal kidneys in animals and humans. After renal damage, OPN expression may be significantly up-regulated in all tubule segments and glomeruli. Studies utilizing OPN gene-deficient mice, antisense-treated or anti-OPN-treated animals have demonstrated that OPN promotes accumulation of macrophages, and may play a role in macrophage-mediated renal injury, but that the effect may be mild and short-lived. On the other hand, OPN has some renoprotective actions in renal injury, such as increasing tolerance to acute ischemia, inhibiting inducible nitric oxide synthase and suppressing nitric oxide synthesis, reducing cell peroxide levels and promoting the survival of cells exposed to hypoxia, decreasing cell apoptosis and participating in the regeneration of cells. In addition, OPN is associated with renal stones, but whether it acts as a promoter or inhibitor of stone formation is controversial. It has been demonstrated that OPN receptors include two families: integrin and CD44. The OPN integrin receptors include alpha(v)beta(3), alpha(v)beta(1), alpha(v)beta(5) and alpha(9)beta(1), and alpha(4)beta(1). In normal human kidneys, standard CD44 is expressed most dominantly. Different OPN functions are mediated via distinct receptors. Parathyroid hormone, vitamin D(3), calcium, phosphate and some cytokines increase OPN expression in vitro or in vivo, whereas female sex hormones and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists decrease OPN expression in some renal damage states.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                April 2004
                08 April 2004
                : 24
                : 2
                : 188-197
                aDivision of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, and bDepartment of Oral Morphology, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan; cKidney Center of PLA, Department of Nephrology, Chinese General Hospital of PLA, Beijing, China
                76758 Am J Nephrol 2004;24:188–197
                © 2004 S. Karger AG, Basel

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                Page count
                Figures: 4, References: 21, Pages: 10
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/76758
                Original Report: Laboratory Investigation

                Cardiovascular Medicine, Nephrology

                CD44, Acute tubular necrosis, Plasma membrane


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