title: Reduced sulfation of chondroitin sulfate but not heparan sulfate in kidneys of diabetic db/db mice.
abstract: Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Trine M
authors.initials: TM
authors.lastname: Reine
authors.forename: Frøy
authors.initials: F
authors.lastname: Grøndahl
authors.forename: Trond G
authors.initials: TG
authors.lastname: Jenssen
authors.forename: Elin
authors.initials: E
authors.lastname: Hadler-Olsen
authors.forename: Kristian
authors.initials: K
authors.lastname: Prydz
authors.forename: Svein O
authors.initials: SO
authors.lastname: Kolset
mesh_terms: D000818:Animals; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D013431:Sulfates / Q000378:metabolism*
chemical_list: D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D013431:Sulfates
keywords: HPLC; chondroitin sulfate; diabetes; disaccharides; heparan sulfate; immunohistochemistry; nephropathy; proteoglycan