Differentiation of smooth muscle phenotypes in mouse mesangial cells.

Smooth muscle alpha-actin (SMA) mRNA, a marker of vascular smooth muscle cells, was identified in the normal glomerular mesangium both in vivo and in vitro. Several populations of mesangial cells were studied to determine if SMA and basement membrane collagen were regulated together. The levels of SMA expression, which could be linked to the stage of differentiation, were different for the differing cell populations. One cell population had high SMA and type IV collagen levels at its early passages. The others expressed both interstitial and basement membrane collagens. The first population developed these phenotypic features at later passages. The levels of SMA and alpha 1(IV) collagen expression were regulated together in concert, whereas the alpha 2(I) collagen levels were expressed inversely to SMA and alpha 1(IV) collagen. Both SMA and type IV collagen were controlled by the methylation states of the cis-regulators; however, type I collagen was mainly regulated by the trans-acting regulators. Treatment with 5-azacytidine converted the cells of a fibroblast-phenotype to a smooth muscle cell-like phenotype. These cell lines may be useful for studying the differentiation process in vitro.