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A multifunctional transcription factor (A1p145) regulates the smooth muscle phenotype in mesangial cells
H Takeoka1, N Iehara, M Uematsu-Yanagita
1Department of Geriatric Medicine, Division of Clinical Bio-regulatory Science, Division of Artificial Kidneys, Faculty of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Kyoto, Sakyo-ku, 606, Japan.
Abstract:
A1p145, a novel DNA binding protein for type IV collagen gene (COL4), has multiple functions including DNA replication factor C and DNA binding for several other genes. To elucidate the mechanisms underlying the differentiation process of mesangial cells (MCs), we investigated the effects of A1p145 on rat MCs. Cells in the early passages showed a smooth muscle-like phenotype such as low cell turnover, high levels of expression for COL4, and smooth muscle alpha-actin (SMA). Cells in the late passages lost their phenotype. The amount of binding activity to COL4 promoter was inversely correlated with the level of COL4 mRNA. Introduction of antisense for A1p145 into late passage cells enhanced the levels of mRNA for COL4 and SMA. The levels of proliferating cell nuclear antigen mRNA were also suppressed. These results suggest that A1p145 is a negative transcription factor for COL4 and may be a phenotypic modulator.