Circadian rhythms of angiogenic factors in skin and wound tissue in per 2-mutant mice

It has recently been reported that circadian gene Period 2 (per2) regulates mRNA expression of vascular endothelial growth factor gene (Vegf) in some tumor cells. It still remains unknown, however, whether per2 has an effect on expression of angiogenic factors during the wound healing process. To investigate the circadian rhythms of angiogenic factors in intact skin and wound tissue in per2-mutant and control mice, we used a skin incision wound model on per2-mutant and control mice, and analyzed circadian rhythms of mRNA levels for several angiogenic factors. Our results show a novel finding that, for some angiogenic factors, the circadian rhythms of mRNA levels in wound tissue exist in per2-mutant as well as in control mice, indicating that some circadian rhythms may be per2-independent. We observed circadian rhythms of per2 and some angiogenic factor mRNAs in control mouse intact skin. The circadian patterns of some angiogenic factors mRNAs in intact skin were altered in per2-mutant mice relative to normal mice, indicating the existence of per2-dependent and independent regulations of angiogenic factors expressions. Correspondence to: Makoto Nogami, Department of Legal Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan, Tel: +81 3 3964 1211; E-mail: [email protected]