Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells.
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.
Wolf
G
G
Renal-Electrolyte Section, University of Pennsylvania, Philadelphia 19104-6144.
Haberstroh
U
U
Neilson
E G
EG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002678:Chimera / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D003893:Desmin / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D011392:Proline / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011863:Radioimmunoassay; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014316:Tritium; D014746:Vimentin / Q000032:analysis
D016895:Culture Media, Serum-Free; D003893:Desmin; D007328:Insulin; D014746:Vimentin; D014316:Tritium; D000804:Angiotensin II; D003094:Collagen; D004247:DNA; D011392:Proline; D015500:Chloramphenicol O-Acetyltransferase