Loss of vascular endothelial growth factor a activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation

摘要: The angiogenic cytokine vascular endothelial growth factor (VEGF)-A plays a central role in both wound healing and tumor growth. In the skin, epidermal keratinocytes are major source of this factor. To study contribution keratinocyte-derived VEGF-A to these angiogenesis-dependent processes, we generated mice which was inactivated specifically keratin 5-expressing tissues. mutant were macroscopically normal, skin capillary system well established, demonstrating that is not essential for angiogenesis during embryonic development. However, full-thickness wounds adult animals appreciably delayed compared with controls, retarded crust shedding appearance blood vessel-free zone underneath newly formed epidermis. When 9,12-dimethyl 1,2-benzanthracene applied as initiator promoter, total 143 papillomas developed 20 23 (87%) control mice. contrast, only three arose 2 17 (12%) mice, whereas rest merely displayed thickening parakeratosis. Mutant also squamous cell carcinomas, 11 carcinomas found seven animals. These data demonstrate dispensable vascularization under physiological conditions, it an important albeit nonessential crucial development 1,2-benzanthracene-induced epithelial tumors.