title: Increased glomerular alpha 1 (IV) collagen expression and deposition in long-term diabetic rats is prevented by chronic glycosaminoglycan treatment.
abstract: Diabetic nephropathy is associated with thickening of the glomerular basement membrane and, in particular, with mesangial matrix expansion. Previous studies have indicated that administration of chemically modified, low-anticoagulant heparins prevents some of the morphologic and physiologic alterations occurring in experimental diabetic nephropathy. The effect of prolonged heparin treatment on the glomerular expression and deposition of alpha 1 (IV) collagen, which is a major component of the mesangial matrix, has not been reported previously. Four groups of rats were studied for 12 months: two control groups and two groups of streptozotocin-diabetic rats. One group in each branch received modified heparin continuously from the induction of diabetes. After 12 months synthesis and deposition of alpha 1 (IV) collagglomerula and adjacent tubuli were determined by nonradioactive in situ hybridization and immunohistochemistry. Mesangial cells were localized by Thy 1.1 staining. Long-term diabetes caused a significant increase in alpha 1 (IV) collagen deposition in the mesangial matrix and a more than 2-fold enhancement of glomerular cell alpha 1 (IV) collagen transcript levels, mainly in mesangial cells. The alpha 1 (IV) collagen mRNA levels of proximal tubular cells and visceral epithelial cells were similarly increased. Chronic treatment of diabetic rats with modified heparin completely prevented the increased alpha 1 (IV) collagen deposition and expression. The increased glomerular deposition of alpha 1 (IV) collagen observed in long-term streptozotocin diabetic rats appears to depend on an increased alpha 1 (IV) collagen synthesis. Because chronic application of low-anticoagulant heparin completely prevents the increased alpha 1 (IV) collagen synthesis by mesangial cells, this result suggests a new therapeutic option for the prevention of diabetic nephropathy in humans.
authors.affiliation: Department of Nephrology, University of Padua, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ceol
authors.forename: A
authors.initials: A
authors.lastname: Nerlich
authors.forename: B
authors.initials: B
authors.lastname: Baggio
authors.forename: F
authors.initials: F
authors.lastname: Anglani
authors.forename: U
authors.initials: U
authors.lastname: Sauer
authors.forename: E
authors.initials: E
authors.lastname: Schleicher
authors.forename: G
authors.initials: G
authors.lastname: Gambaro
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004334:Drug Administration Schedule; D006025:Glycosaminoglycans / Q000008:administration & dosage* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006025:Glycosaminoglycans; D012333:RNA, Messenger; D006493:Heparin; D003094:Collagen