BASEMENT-MEMBRANE CHONDROITIN SULFATE PROTEOGLYCAN ALTERATIONS IN A RAT MODEL OF POLYCYSTIC KIDNEY-DISEASE

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 Marke d dilation of distal tubules and collecting ducts was observed by 4 da ys with phenol II treatment, but the morphology returned to normal aft er 7 days of subsequent normal diet. Staining of tissue sections with two mouse monoclonal antibodies to a recently described basement membr ane chondroitin sulfate proteoglycan (BM-CSPG) core protein was marked ly diminished in the basement membranes of dilated cystic tubules. Red uction in staining was evident as early as 2 days. During recovery, BM -CSPG increased in tubular basement membranes and returned to normal a fter 7 clays. Staining with a polyclonal antibody to chondroitin sulfa te chains confirmed these changes in cystic tubule basement membranes. During the recovery stage, interstitial chondroitin sulfate (represen ting a CSPG other than BM-CSPG) was greatly increased around these tub ules, along with the glycoprotein fibronectin. Staining with antibody to a basement membrane heparan sulfate proteoglycan core protein relat ed to perlecan did not diminish but rather stained affected tubules in tensely, whereas laminin, on the other hand was apparently diminished in the basement membranes of the cystic tubules. Type IV collagen stai ning did not change through disease onset or recovery. These results s uggest that BM-CSPG, which was rapidly altered in distribution through the onset and recovery phases, may be a sensitive marker of the cysti c state, and in addition, the expression of basement membrane proteogl ycans may be specifically, and separately regulated in this disease