Demonstration of DNA replication factor C in human glomerular lesions.
Glomerulosclerosis is a common pathological finding in many human glomerular 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 promoter of the alpha 1 and alpha 2 type IV collagen genes was cloned. MSW was found to be identical to a large subunit (Alp145) of DNA replication factor C. These findings suggest that MSW may have important functions in mesangial cell proliferation and type IV collagen synthesis, both of which are prominent findings in glomerulosclerosis. In the present study, we report that augmented expression of MSW protein in human glomerular diseases that exhibit glomerulosclerosis (IgA nephropathy, membranoproliferative glomerulonephritis, and focal glomerulosclerosis). Minimal expression of MSW protein was observed in human glomerular diseases that rarely show glomerulosclerosis (membranous nephropathy, and minimal change nephrotic syndrome). There was a significant correlation between the levels of MSW expression and type IV collagen expression. Elevated expressions of both proliferating cell nuclear antigen and MSW were also observed in most patients with proliferative glomerular diseases. These studies suggest that MSW protein plays a regulatory role in the development of mesangial cell proliferation and matrix expansion during progression of glomerular injuries.
Komatsu
T
T
Department of Internal Medicine, Amagasaki Prefectural Hospital, Japan.
Kanatsu
K
K
Kuze
K
K
Iehara
N
N
Takeoka
H
H
Yamada
Y
Y
Kita
T
T
Doi
T
T
D000328:Adult; D003094:Collagen / Q000032:analysis; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000378:metabolism*; D018398:Homeodomain Proteins; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000032:analysis
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; C109086:MSW protein, human; C484646:MSW protein, mouse; D015778:Minor Histocompatibility Antigens; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D003094:Collagen; D051818:Replication Protein C