engleski

Changes in expression of intermediate filaments, factors of vasculogenesis and receptor of advanced glycation end products are observed during normal human nephronogenesis and podocyte differentiation

Objectives: Normal course of nephrogenesis and podocyte differentiation are essential for normal morphology and function of human kidney. Information about human kidney development is scarce and contradictory. Present study analyzes the ultrastructural and immunohistochemical characteristics of developing nephrons, from metanephric cap stage through stages of renal vesicle, comma and S- shaped bodies, glomerular capillary and maturing glomeruli. Changes in morphology and intracellular protein content during maturation of human podocytes are described. Methods: Human kidney tissues between the 7th and 38th developmental week were analyzed using double immunofluorescence method and electron microscopy. Primary antibodies included intermediate filaments vimentin and cytokeratin 10 (CK10), factors of vasculogenesis CD31 and VEGF, and receptor of advanced glycation end products (RAGE). Results: During the investgated period, human nephronogenesis underwent transformation of metanephric cap into the maturing glomeruli. With progression of development, vimentin expression increased in gomerules, including podocytes and Bowman’s capsule. CK10 was expressed in ampulla and metanephric cap, while during later nephronogensis it gradually decreased. CD31 was increasingly strong in developing glomerular vessels, while VEGF characterized population of differentiating podocytes and cells of Bowman’s capsule. RAGE was strongly positive in some metanephric cup and ampullar cells, diffusely distributed in C- and S-shaped bodies, while restricted to podocytes in maturing glomeruli. Ultrastructurally, we detected filaments in podocyte cytoplasm and their accumulation at adherent junctions between neighboring podocytes. Conclusions: Transition of metanephric cap cells into renal vesicle were associated with early CK10 and RAGE expression that accorded with mesenchymal-to- epithelial transformation of metanephric mesenchyme. Reverse process of epithelial-to mesenchymal transition, appearing during further nephronogenesis was associated with increase of vimentin expression, while CD31 and VEGF expression enhanced glomerular vasculogenesis. Later on, restriction of RAGE expression to podocyte population indicates importance of RAGE in normal metabolism and apoptosis of podocytes.

nephrogenesis; podocyte; RAGE; intermediary filaments; vasculogenesis; human embryo

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