Models for Studies of Proteoglycans in Kidney Pathophysiology

Proteoglycans (PGs) impact many aspects of kidney health and disease. Models that permit genetic dissection of PG core protein and glycosaminoglycan (GAG) function have been instrumental to understanding their roles in the kidney. Matrix-associated PGs do not serve critical structural roles in the organ, nor do they contribute significantly to the glomerular barrier under normal conditions, but their abnormal expression influences fibrosis, inflammation, and progression of kidney disease. Most core proteins are dispensable for nephrogenesis (glypican-3 being an exception) and for maintenance of function in adult life, but their loss alters susceptibility to experimental kidney injury. In contrast, kidney development is exquisitely sensitive to GAG expression and fine structure as evidenced by the severe phenotypes of mutants for genes involved in GAG biosynthesis. This article reviews PG expression in normal kidney and the abnormalities caused by their disruption in mice and man.