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(American Journal of Pathology. 2004;165:1653-1662.)
© 2004 American Society for Investigative Pathology

Effects of Angiotensin II Receptor Signaling during Skin Wound Healing

Hikaru Takeda, Yohtaro Katagata, Yutaka Hozumi and Shigeo Kondo

From the Department of Dermatology, Yamagata University School of Medicine, Yamagata, Japan

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 (AT1) blocker suppressed keratinocyte re-epithelization and angiogenesis during skin wound healing in rats. Immunoprecipitation and Western blot analysis indicated the existence of AT1 and AngII type-2 receptor (AT2) in cultured keratinocytes and myofibroblasts. In a bromodeoxyuridine incorporation study, induction of AT1 signaling enhanced the incorporation into keratinocytes and myofibroblasts. Wound healing migration assays revealed that induction of AT1 signaling accelerated keratinocyte re-epithelization and myofibroblasts recovering. In these experiments, induction of AT2 signaling acted vice versa. Taken together, our study suggests that skin wound healing is regulated by balance of opposing signals between AT1 and AT2.




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