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Analysis of ciliated podocytes during normal human glomerular development and in nephrotic kidneys

Introduction: Primary cilia are non-motile sensory organelles involved in the control of different cellular processes, including cell differentiation. The role of primary cilia has been implicated in numerous cystic kidney diseases. By now, primary cilia have been detected on the surfaces of tubular cells and collecting ducts in developing and postnatal human kidneys. In the present study we analyze appearance and percentage of primary cilia on the surfaces of developing human healthy and nephrotic podocytes. Material and methods: Kidney tissue were dissected from human conceptuses 8th-38th postovulatory week old, postnatal healthy and nephrotic syndrome of the Finnish type (CNF) kidneys. They were stained by double immunofluorescent technique, using α- tubulin as primary cilia marker and DAPI as nuclear marker. Cilia were counted on cell surfaces and their percentage was calculated using Kruskal–Wallis test, followed by Dunns post-hoc test. Ultrastructural characteristics of podocytes were analyzed by transmission electron microscopy. Results: Between the 8th and 10th developmental week, population of metanephric cup cells contained 24% of ciliated cells, immature glomeruli 47% and Bownam’s capsule cells (parietal podocytes) 26%. Percentage of ciliated podocytes decreased to 10% in the 38th week and then to 3% in postnatal period. Number of ciliated cells in Bowman’s capsule first increased to 32% by the 22nd developmental week, and postnatally decreased to 16%. Compared to healthy kidneys, CNF podocytes showed increased number of ciliated podocytes (12%) and Bowman’s capsule cells (19%). Conclusions: Prospective human podocytes contain primary cilia already at the metanephric cup stage. During development, number of ciliated podocytes decreases in accordance with podocyte differentiation, while Bowman’s capsule cells retain higher percentage of ciliated cell, thus indicating their potential in podocyte regeneration. Compared to healthy kidneys, both cell populations of CNF kidneys display higher percentage of primary cilia, pointing to their incomplete maturation.

human kidney development ; primary cilia ; podocytes ; congenital nephrotic syndrome

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