DEMONSTRATION OF DNA-REPLICATION FACTOR-C IN HUMAN GLOMERULAR-LESIONS

Glomerulosclerosis is a common pathological finding in many human glom erular diseases that ultimately leads to end-stage kidney disease. The regulatory mechanism that controls mesangial proliferation as well as accumulation of mesangial matrix: however, is not known. Recently, a protein factor (MSW) which binds to the specific sequence of the promo ter of the alpha(1) and alpha(2) type IV collagen genes was cloned. MS W was found to be identical to a large subunit (Alp145) of DNA replica tion factor C. These findings suggest that MSW may have important func tions in mesangial cell proliferation and type IV collagen synthesis, both of which are prominent findings in glomerulosclerosis. In the pre sent study, we report that augmented expression of MSW protein in huma n glomerular diseases that exhibit glomerulosclerosis (IgA nephropathy , membranoproliferative glomerulonephritis, and focal glomeruloscleros is). Minimal expression of MSW protein was observed in human glomerula r diseases that rarely show glomerulosclerosis (membranous nephropathy , and minimal change nephrotic syndrome). There was a significant corr elation between the levels of MSW expression and type IV collagen expr ession. Elevated expressions of both proliferating cell nuclear antige n and MSW were also observed in most patients with proliferative glome rular diseases. These studies suggest that MSW protein plays a regulat ory role in the development of mesangial cell proliferation and matrix expansion during progression of glomerular injuries.