Coexpression of AT1 and AT2 receptors by human fibroblasts is associated with resistance to angiotensin II.
Angiotensin II (AngII) is considered as a cytokine-like factor displaying a variety of proinflammatory and profibrotic cellular effects. Most of these effects seem mediated by AT1 signaling, whereas AT2 expression and function in adult human cells remain unclear. We have studied AT1 and AT2 expression in different human adult fibroblasts types and analyze their response to AngII. AngII did not induce thymidine incorporation, apoptosis nor collagen gene or protein expression in human fibroblasts. Specific AT1 or AT2 inhibitors did not modify this apparent resistance to AngII. We found abundant expression of both AT1 and AT2 receptors in all human fibroblasts studied, whereas vascular smooth muscle cells (VSMC) which only expressed AT1 receptor, displayed a clear AT1-dependent proliferative response to AngII. These data demonstrate that cultured human adult fibroblasts express both AT1 and AT2 receptor types and this phenomenon is associated with a lack of growth or collagen synthesis responses to AngII.
Galindo
María
M
Servicio de Reumatología y Unidad de Investigación, Hospital 12 de Octubre, Carretera de Andalucía Km 5.4, 28041 Madrid, Spain.
Santiago
Begoña
B
Palao
Guillermo
G
Gutierrez-Cañas
Irene
I
Ramirez
Juan Carlos
JC
Pablos
José Luis
JL
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011347:Procollagen / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D024042:Collagen Type I; D016895:Culture Media, Serum-Free; D007093:Imidazoles; D011347:Procollagen; D011725:Pyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan