title: Targeted overexpression of Angptl6/angiopoietin-related growth factor in the skin promotes angiogenesis and lymphatic vessel enlargement in response to ultraviolet B.
abstract: Angiogenesis is required for physiological tissue repair processes, such as cutaneous wound healing. However, recent studies indicate that endogenous angiogenic factors may enhance photo-induced skin alterations in response to experimental ultraviolet (UV)-B exposure. Angiopoietin-related growth factor (AGF), also known as angiopoietin-like protein 6 (Angptl6), is known to promote new blood vessel formation and vascular hyperpermeability. Importantly, epidermal overexpression of Angptl6/AGF in mice promotes wound healing in the skin. However, it remains unclear whether overexpression of Angptl6/AGF facilitates tissue repair processes in response to UV-B irradiation. To test this hypothesis, we subjected Angptl6/AGF transgenic mice to acute or chronic UV-B exposure. Surprisingly, transgenic mice showed enhanced photosensitivity to subthreshold doses of UV-B that did not induce skin alterations in wild-type littermates. Marked enlargement of blood vessels was observed after a single exposure to UV-B in Angptl6/AGF transgenic mice, although no epidermal changes were observed. Chronic UV-B exposure over 14 weeks promoted cutaneous skin damage in Angptl6/AGF transgenic mice, whereas wild-type mice showed little or no macroscopic skin alteration. In addition to pronounced angiogenesis and epidermal hyperplasia, marked enlargement of dermal lymphatic vessels was observed in UV-B-exposed Angptl6/AGF transgenic mice. Electron microscopy analysis further revealed that the number and size of collagen bundles in the dermis was markedly reduced after chronic UV-B exposure in Angptl6/AGF transgenic mice. Taken together, these results indicate that ectopic expression of Angptl6/AGF in mice likely promotes UV-B-induced skin alterations, and that angiogenesis could be a therapeutic target in prevention of skin photo-aging.
authors: Department of Dermatology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Hidenori
authors: H
authors: Okazaki
authors: Satoshi
authors: S
authors: Hirakawa
authors: Masachika
authors: M
authors: Shudou
authors: Yoshiki
authors: Y
authors: Nakaoka
authors: Yuji
authors: Y
authors: Shirakata
authors: Keishi
authors: K
authors: Miyata
authors: Yuichi
authors: Y
authors: Oike
authors: Koji
authors: K
authors: Hashimoto
authors: Koji
authors: K
authors: Sayama
mesh_terms: D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D010787:Photosensitivity Disorders / Q000209:etiology / Q000235:genetics; D012867:Skin / Q000033:anatomy & histology / Q000098:blood supply* / Q000528:radiation effects*; D014466:Ultraviolet Rays; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics / Q000502:physiology / Q000528:radiation effects
chemical_list: D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C477602:Angptl6 protein, mouse