During nephrogenesis, basement membrane genes are expressed in a coordinate fashion in different portions of the nephron. After nephrogenesis is complete and during adult life, matrix proteins are synthesized at low levels, presumably representing on-going replacement of basement membrane and mesangial matrix. A common feature of response to injury or inflammation by many tissues is the increased deposition of matrix proteins. The kidney is exquisitely sensitive to malfunction as a consequence of scarring stemming from the repair process. Whereas many mesenchymal tissues (skin, bone, muscle, liver) and certain epithelial tissues (spleen intestine) can maintain function despite a degree of structural disorganization, normal renal function is predicated on the precise tissue structure. Thus, scarring anywhere along the nephron threatens the filtration process. Progressive renal disease of many etiologies is characterized by cellular proliferation and increased accumulation of a cellular material within the glomerular mesangium and the renal interstitium. The purpose of these studies is to determine the molecular mechanisms responsible for the regulation of extracellular matrix proteins, to explore inducible factors that modulate mitogenesis and cellular matrix protein production such as hormones, autacoids, cytokines, and growth factors, and to develop novel therapeutic strategies to prevent progressive fibrosis and sclerosis.
