Mice engineered to produce excess amounts of a protein involved in blood vessel and skin cell growth are super healers, suggesting a new approach to treating wounds in humans.



The mice were engineered to produce a growth factor, called angiopoietin-related growth factor, in their skin cells.



Researchers from Keio University and Kumamoto University in Japan found that the AGF mice had not only increased numbers of micro blood vessels in the skin but also thickened epidermal layers and rapid wound closure.


The epidermis is the most superficial layer of the skin and provides the first barrier of protection from invasion by foreign substances into the body. An important role of the epidermis in wound management is wound closure.



Reporting in the online edition of the Proceedings of the National Academy of Sciences, the researchers say that AGF directly enhances the growth of epidermal keratinocytes. Keratinocytes are cells that compose skin and prevent entry of toxic substances from the environment.



To determine the rapidity of wound closure, the researchers made a two millimeter hole in the center of both ears of the AGF mice and controls by using a metal ear punch. They also amputated ears and tails from some of the mice five millimeters from the tip of the tail or five millimeters from the edge of the ears.



Analysis of ear tissues from selected transgenic mice revealed that AGF was in the epidermal layer, whereas there was no AGF expression in either the epidermis or dermis of control mice.



The researchers also found significant numbers of micro vessels in the dermis, suggesting that AGF promotes angiogenesis — the formation of new blood cells. The researchers also found a markedly thickened epidermis and thickened ears in the AGF mice compared with controls.



“Based on our findings that AGF is expressed abundantly in various blood cells,” the researchers report, AGF may “contribute to repair of wounding sites through promoting proliferation of keratinocytes and angiogenesis.”



The biological functions of AGF in both keratinocytes and vascular cells could be exploited in novel therapeutic strategies for wound care and epidermal regenerative medicine.



Future research will likely probe deeper into AGF’s role in wound healing by examining mice engineered to be deficient in the growth factor.

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