A MULTIFUNCTIONAL TRANSCRIPTION FACTOR (A1P145) REGULATES THE SMOOTH-MUSCLE PHENOTYPE IN MESANGIAL CELLS

Alp145, a novel DNA binding protein for type IV collagen gene (COL4), has multiple functions including DNA replication factor C and DNA bind ing for several other genes. To elucidate the mechanisms underlying th e differentiation process of mesangial cells (MCs), we investigated th e effects of Alp145 on rat MCs. Cells in the early passages showed a s mooth muscle-like phenotype such as low cell turnover, high levels of expression for COL4, and smooth muscle a-actin (SMA). Cells in the lat e passages lost their phenotype. The amount of binding activity to COL 4 promoter was inversely correlated with the level of COL4 mRNA. Intro duction of antisense for Alp145 into late passage cells enhanced the l evels of mRNA for COL4 and SMA. The levels of proliferating cell nucle ar antigen mRNA were also suppressed. These results suggest that Alp14 5 is a negative transcription factor for COL4 and may be a phenotypic modulator. (C) 1998 Academic Press.