Summary
The pathogenic role of the tubular basement membrane was studied in polycystic kidney disease (PKD) induced by diphenylthiazole (DPT) or its major urinary metabolite, phenol II, and in cyst-derived cells from human autosomal dominant PKD kidneys. DPT induced, in rats, progressive, but reversible cystic change of collecting tubules (CDs), characterized by thickening of the tubular basement membrane with marked reduction of the de novo synthesis of sulfated proteoglycans. The phenol II was administered for 4 days to determine the sequence of tubular cell and BM changes in the development of PKD. At day one, 12% of CDs were cystic and their BMs were altered. Over the 4 day interval, BMs remained structurally altered and cystic change increased progressively. Cell proliferation was not detected until day 2 and occurred both in cystic and in non-cystic renal zones; it did not increase as cystic change progressed. By immunofluorescence, there was a decrease in anti-heparin sulfate proteoglycan core protein reactivity and an increase in anti-fibronectin reactivity of the extracellular matrices of cystic tubules. In the in vitro studies, the growth rate, cell doubling time, and end cell number of cyst-derived autosomal dominant polycystic kidney disease (ADPKD) and normal human renal epithelial (NK) cells were the same; moreover, ADPKD cells did not exhibit any in vitro features of transformed cells. Post-confluent NK and ADPKD cells in vitro elaborated distinct BMs. By electron microscopy, BMs of NK cells were of uniform thickness with a regular pattern of ruthenium red (RR) binding sites indicative of proteoglycans. In contrast, BMs of ADPKD cells were less dense, thicker, and lacked RR sites; immunofluorescent reactivity to anti-HS-PG core protein was uneven and decreased while reactivity to anti fibronectin was increased. The findings suggest that BM components are in a dynamic metabolic state, capable of rapid modulation, and that PKD may be due to a defect in the synthesis/degradation of one or more basement membrane components, resulting in faulty tubular morphogenesis.
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© 1991 Springer Japan
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Carone, F.A., Kanwar, Y.S. (1991). Pathobiology of Tubular Basement Membranes in Renal Cystic Disease. In: Hatano, M. (eds) Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-35158-1_85
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DOI: https://doi.org/10.1007/978-3-662-35158-1_85
Publisher Name: Springer, Berlin, Heidelberg
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