Angiotensin II stimulates proliferation of primary human keratinocytes via a non-AT1, non-AT2 angiotensin receptor.
Angiotensin II is a hormone with long known cardiovascular actions. Recent studies revealed an additional role for angiotensin II in the regulation of cell proliferation. This study was performed to clarify whether skin is a target organ for these novel angiotensin actions. Radioligand binding studies identified a high-affinity angiotensin receptor on human primary keratinocytes in vitro with a Kd of 4.5 nM and a Bmax of 0.12 nM. Competition experiments with losartan and PD 123177 revealed that this receptor was not of the AT1- nor the AT2-subtype. Stimulation of human keratinocytes with angiotensin II (10(-10) to 10(-5) M) led to a dose dependent increase in 3H-thymidine incorporation, indicating that the keratinocyte receptor mediates a mitogenic effect. This effect is comparable at 10(-9) M to stimulation of keratinocytes by EGF (50ng/ml) and FGF (50ng/ml). These results demonstrate for the first time a possible physiological role for angiotensin II in human skin involving the regulation of keratinocyte proliferation.
Steckelings
U M
UM
Department of Dermatology, Virchow Klinikum, Humboldt Universität, Berlin, Germany.
Artuc
M
M
Paul
M
M
Stoll
M
M
Henz
B M
BM
D000804:Angiotensin II / Q000494:pharmacology*; D001667:Binding, Competitive; D002455:Cell Division; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects*; D008024:Ligands; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena
D008024:Ligands; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor