Effects of angiotensin II receptor signaling during skin wound healing.
The tissue angiotensin (Ang) system, which acts independently of the circulating renin Ang system, is supposed to play an important role in tissue repair in the heart and kidney. In the skin, the role of the system for wound healing has remained to be ascertained. Our study demonstrated that oral administration of selective AngII type-1 receptor (AT(1)) blocker suppressed keratinocyte re-epithelization and angiogenesis during skin wound healing in rats. Immunoprecipitation and Western blot analysis indicated the existence of AT(1) and AngII type-2 receptor (AT(2)) in cultured keratinocytes and myofibroblasts. In a bromodeoxyuridine incorporation study, induction of AT(1) signaling enhanced the incorporation into keratinocytes and myofibroblasts. Wound healing migration assays revealed that induction of AT(1) signaling accelerated keratinocyte re-epithelization and myofibroblasts recovering. In these experiments, induction of AT(2) signaling acted vice versa. Taken together, our study suggests that skin wound healing is regulated by balance of opposing signals between AT(1) and AT(2).
Takeda
Hikaru
H
Department of Dermatology, Yamagata University, School of Medicine, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan. hitakeda@med.id.yamagata-u.ac.jp
Katagata
Yohtaro
Y
Hozumi
Yutaka
Y
Kondo
Shigeo
S
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004396:Coloring Agents / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000473:pathology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
D004396:Coloring Agents; D011945:Receptors, Angiotensin; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D001973:Bromodeoxyuridine