DIFFERENTIATION OF SMOOTH-MUSCLE PHENOTYPES IN MOUSE MESANGIAL CELLS

Smooth muscle alpha-actin (SMA) mRNA, a marker of vascular smooth musc le cells, was identified in the normal glomerular mesangium both in vi vo and in vitro. Several populations of mesangial cells were studied t o determine if SMA and basement membrane collagen were regulated toget her. 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 e arly passages. The others expressed both interstitial and basement mem brane collagens. The first population developed these phenotypic featu res at later passages. The levels of SMA and alpha 1(IV) collagen expr ession were regulated together in concert, whereas the alpha 2(I) coll agen levels were expressed inversely to SMA and alpha 1(IV) collagen. Both SMA and type IV collagen were controlled by the methylation state s of the cis-regulators; however, type I collagen was mainly regulated by the trans-acting regulators. Treatment with 5-azacytidine converte d the cells of a fibroblast-phenotype to a smooth muscle cell-like phe notype. These cell lines may be useful for studying the differentiatio n process in vitro.