Diabetes results in structural alteration of chondroitin sulfate/dermatan sulfate in the rat kidney: effects on the binding to extracellular matrix components.

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 β1-3 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.