Renal mesangial cell proliferation regulates proteoglycan levels and sulfation

grantor: University of TorontoThe kidney responds to injury by progression through a series of stages that can lead to healing of the kidney; but when the insult is repetitive these same stages lead to kidney disease. Glomerulonephritis is a common form of human kidney disease that has been studied extensively using rat kidney disease models. We have sought to understand how the stage of compensatory growth of glomerular mesangial cells influences the mesangial cell production of proteoglycans. Proteoglycans may play a role in regulating glomerulonephritis by regulating the proliferation of mesangial cells and the composition of the mesangial matrix. We have observed that for cultured rat renal mesangial cells (RMCs) the proliferative state regulates the levels and sulfation of proteoglycans. In particular, cell layer and medium proteoglycan levels are lower in randomly cycling RMCs than in relatively quiescent RMCs, and one proteoglycan--biglycan--has enhanced sulfation in randomly cycling RMCs compared to quiescent RMCs. The effects on proliferation of biglycan levels and sulfation do not influence the ability of TGF-$\beta$ to increase biglycan mRNA and protein levels, indicating different pathways of regulation. Our results provide more insight into understanding the role of mesangial cell during the proliferative and fibrotic phases of glomerulonephritis.M.Sc