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American Journal of Pathology, Vol 144, 612-621, Copyright © 1994 by American Society for Investigative Pathology

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Basement membrane chondroitin sulfate proteoglycan alterations in a rat model of polycystic kidney disease

T Ehara, FA Carone, KJ McCarthy and JR Couchman
Department of Cell Biology, University of Alabama at Birmingham 35294- 0019.

Alterations in basement membrane components, notably proteoglycans, in a rat model of polycystic kidney disease have been investigated. Rats were fed phenol II (2-amino-4-hydroxyphenyl-5-phenyl thiazole) for 4 days and then changed to normal diet for a 7-day recovery period. Marked dilation of distal tubules and collecting ducts was observed by 4 days with phenol II treatment, but the morphology returned to normal after 7 days of subsequent normal diet. Staining of tissue sections with two mouse monoclonal antibodies to a recently described basement membrane chondroitin sulfate proteoglycan (BM-CSPG) core protein was markedly diminished in the basement membranes of dilated cystic tubules. Reduction in staining was evident as early as 2 days. During recovery, BM-CSPG increased in tubular basement membranes and returned to normal after 7 days. Staining with a polyclonal antibody to chondroitin sulfate chains confirmed these changes in cystic tubule basement membranes. During the recovery stage, interstitial chondroitin sulfate (representing a CSPG other than BM-CSPG) was greatly increased around these tubules, along with the glycoprotein fibronectin. Staining with antibody to a basement membrane heparan sulfate proteoglycan core protein related to perlecan did not diminish but rather stained affected tubules intensely, whereas laminin, on the other hand, was apparently diminished in the basement membranes of the cystic tubules. Type IV collagen staining did not change through disease onset or recovery. These results suggest that BM-CSPG, which was rapidly altered in distribution through the onset and recovery phases, may be a sensitive marker of the cystic state, and in addition, the expression of basement membrane proteoglycans may be specifically and separately regulated in this disease.

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