Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells

Abstract

A murine mesangial cell line (MMC) was established from the glomeruli of SJL mice to study the influence of angiotensin II (ANG II) on their growth and function in a serum-free culture. Murine mesangial cells exhibit the phenotypic characteristics of mesangial cells, including staining for desmin, vimentin, Thy 1, and types I and IV collagen by immunofluorescence. The addition of daily doses of 10(-6) to 10(-11) mol/l ANG II to MMCs also induced their proliferation in serum-free media. This effect on growth was independent of the presence of insulin in the media, and was receptor mediated, because the specific ANG II-receptor antagonist DuP 753 abolished proliferative growth. Angiotensin II also stimulated mainly the biosynthesis of type I collagen in our MMCs. Transfection of MMCs with chimeric genes containing enhancer/promoter elements for alpha 2(I) and alpha 1(IV) collagens linked to a chloramphenicol acetyltransferase reporter demonstrated that the stimulatory effect of ANG II for type I depends, at least to some extent, on an increase in transcription. These findings indicate collectively that ANG II in serum-free cultures can be a paracrine catalyst for the growth and biosynthesis of type I collagen in mesangial cells.