A novel transcription factor is correlated with both glomerular proliferation and sclerosis in the rat renal ablation...

Glomerular accumulation of the extracellular matrix (ECM) with subsequent sclerosis is a common finding in most progressive renal diseases. Recently MSW (Mouse South Western) protein was cloned by its ability to bind the bidirectional promoter of the collagen IV genes. This protein was also reported as the large subunit of the DNA replication complex A1, as well as the promoter binding protein of corticotropin-releasing hormone and the angiotensinogen gene. To investigate the mechanism of accumulation of the ECM as it relates to glomerular cellular events, the expression of MSW protein was studied in the remnant kidney model. Progressive expression of MSW protein was found in the glomerular sclerotic lesion at week 4 and at later time points after renal ablation. The expression of proliferating cell nuclear antigen (PCNA) and type IV collagen was also correlated with the expression of MSW protein by immunofluorescence. RNA dot blot analysis also showed that the expression of MSW mRNA was increased at week 7 in association with the augmented expression of type IV collagen. These results, taken together, suggest that MSW protein plays an important role in the regulation of type IV collagen gene expression in vivo and may contribute to glomerular cell proliferation and the development of glomerulosclerosis.