engleski

EXPRESSION OF NOTCH2, WNT4 AND SNAIL IN DEVELOPING AND HEALTHY POSTNATAL HUMAN KIDNEYS AND IN PATHOLOGICALLY CHANGED KIDNEYS AFFECTED BY CNF AND FSGS

Introduction: During early human kidney development, metanephric mesenchyme cells undergo mesenchymal–to–epithelial transition (MET). In the S-shape nephron, cells of the proximal nephron differentiate into podocytes and parietal epithelial cells (PECs). Near the vascular glomerular pole, PECs share podocyte markers and ultrastructure. While podocytes are unique terminally differentiated cells, PECs form a simple squamous epithelium. Pathologically changed kidneys are characterized by the proliferation and detachment of podocytes and PECs, and the appearance of cellular bridges between them. We analyzed the expression of Notch2, WNT4 and Snail in developing and postnatal human kidneys, in focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome of the Finnish type (CNF). Material and methods: Expression of Notch2, WNT4 and Snail was analyzed in sections of 10 human conceptuses 8 to 38 weeks old, in 3 healthy postnatal kidneys and in 7 CNF and FSGS samples, using immunohistochemistry and electron microscopy (EM). Results: In developing kidneys, WNT4 expression increased moderately in podocytes and strongly in PECs, while in CNF and FSGS kidneys decreased in both cell populations. Notch2 was widely expressed in the developing kidneys, moderately in podocytes and strongly in PECs. In CNF, expression of Notch2 increased, while it decreased in FSGS. Snail was expressed moderately in early nephrogenesis, while in later development Snail increased only in PECs. In CNF and FSGS kidneys Snail increased both in the podocytes and PECs. EM showed cytoplasmic processes between podocytes and PECs in developing and healthy kidneys, in CNF and FSGS. Conclusions: Developmental expression of WNT4, Notch2 and Snail indicate their role in MET and nephrogenesis of human kidneys, while changed expression pattern characterizes kidneys affected by CNF and FSGS. Cellular bridges characterize both developing podocytes and PECs, while they multiply in CNF and FSGS kidneys.

human kidney development, WNT4, Snail, Notch2, kidney pathology

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