Proteoglycans in primary human endothelial cells and in the mouse kidney

Abstract

In this study we investigate the role of proteoglycans (PGs) in primary human endothelial cells (HUVECs) and in mouse kidney. The PGs exhibit multiple functions by interactions of their glycosaminoglycan (GAG) chains with other partner molecules. Posttranslational modifications of these GAGs, including sulfation, are critical for their binding properties. Such changes may play an important role in the development of diabetic complications. In particular, the role of heparan sulfate (HS) PGs has received much attention in earlier studies.<br><br> Our studies demonstrated changes in HSPG expression and structure in HUVECs cultured in diabetic conditions. Additionally, we identified serglycin, a chondroitin sulfate (CS) / dermatan sulfate (DS) PG, as a prominent PG in these cells. We found serglycin located in intracellular vesicles colocalized with the chemokine CXCL-1, suggesting a role in endothelial storage and secretion of partner molecules. Both inflammatory stimuli and proliferative status affected serglycin expression and cellular localization, which may have impact on endothelial cells in inflammation and angiogenesis. <br><br> It has been suggested that reduced sulfation of HSPGs is implicated in the impaired renal filtration of diabetic nephropathy. We compared kidneys from diabetic db/db mice to healthy db/+ controls and found no effect on HSPG expression nor structure. A novel finding however, was a reduced sulfation and altered structure of CS/DS PGs, suggesting a role for CS/DS in the development of diabetic complications. <br><br> Taken together, our results show an alteration in PG expression and structure both in the vasculature and the kidneys. These findings may prove relevant to studies on diabetes and its complications.