Angiotensin II Stimulates the Proliferation and Biosynthesis of Type I Collagen in Cultured Murine Mesangial Cells

Am J Pathol. 1992 Jan;140(1):95-107.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Cell Division / drug effects
  • Cell Line, Transformed
  • Cells, Cultured
  • Chimera / genetics
  • Chloramphenicol O-Acetyltransferase / genetics
  • Collagen / analysis
  • Collagen / biosynthesis*
  • Collagen / genetics
  • Culture Media, Serum-Free / pharmacology
  • DNA / genetics
  • Desmin / analysis
  • Dose-Response Relationship, Drug
  • Fluorescent Antibody Technique
  • Glomerular Mesangium / chemistry
  • Glomerular Mesangium / cytology*
  • Glomerular Mesangium / metabolism
  • Insulin / pharmacology
  • Mice
  • Phenotype
  • Proline / metabolism
  • Promoter Regions, Genetic / genetics
  • Radioimmunoassay
  • Transcription, Genetic / drug effects
  • Transfection
  • Tritium
  • Vimentin / analysis

Substances

  • Culture Media, Serum-Free
  • Desmin
  • Insulin
  • Vimentin
  • Tritium
  • Angiotensin II
  • Collagen
  • DNA
  • Proline
  • Chloramphenicol O-Acetyltransferase