Journal
GLYCOBIOLOGY
Volume 21, Issue 7, Pages 960-972Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwr029
Keywords
chondroitin sulfate; dermatan sulfate; diabetes; E-disaccharide unit; extracellular matrix components
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Funding
- Department of Science and Technology, New Delhi, India [SR/SO/HS-28/2009]
- Indian Council of Medical Research (ICMR), New Delhi, India
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Chondroitin sulfate (CS)/dermatan sulfate (DS) is a group of sulfated polymers, which play an essential role in various biological phenomena. In the kidney, they are present in small but significant amounts. Studies on their structure-function relationship in the kidney and their changes during diabetic conditions have not been rigorously looked into, which is the focus of this paper. The CS/DS content decreased significantly (14%) during diabetic conditions. This was accompanied by a decrease in the CS/heparan sulfate ratio. Disaccharide composition analysis revealed fine structural changes especially with respect to the E unit [glucuronic acid beta 1-3 N-acetyl d-galactosamine (4,6-O-sulfate)] and the degree of sulfation. The mRNA expression levels of major enzymes involved in the synthesis of the E-disaccharide unit showed a decrease during diabetes. The changes in CS/DS had implications on ligand-binding properties when tested in vitro for binding to major extracellular matrix (ECM) components such as type IV collagen, laminin and fibronectin. Thus, this study provides insights into the structure-function relationship of CS/DS in the kidney during diabetes and alterations of which could aggravate conditions such as diabetic nephropathy by virtue of them being a part of ECM components.
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