Plastic Surgery Research Council

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E2f1 Represses M1 And M2 Macrophages Transformation To Effect Wound Healing Process
Min Wu, PHD,MD, Hui Xiao, Master, Changchun Yang, Master, Zhen Yi, Master, Pei Deng, MD, Haiping Wang, MD, Ning Zeng, Phd, MD, Yiping Wu, Phd, MD.
Tongji Hospital, Wuhan, China.

PURPOSE: Wound healing is a complex process, which is classically divided into inflammation, proliferation and remodeling phases. Macrophages play a key role in wound healing. M1 macrophages mediate tissue damage and initiate the inflammatory response in the early stages of wound healing. M2 phenotype promotes wound healing via formation of a highly vascularized, cellular granulation tissue and scar tissues. The phenotype of polarized M1-M2 macrophage can, to some extent, be reversed in vitro and in vivo. It is not clear whether the mechanism of this switch involves the recruitment of circulating precursors or the reeducation of cells in situ. In our previous study, we found that E2F1-null (E2F1-/-) mice have enhanced expression of macrophages in the border zone of the skin wound at day 7 post-surgery. However, whether E2F1 mediates the M1-M2 switch during the wound healing process is not known.
METHODS: Skin wounds were surgically induced in E2F1-/- mice and the WT littermate. At 2th and 7th day after surgery, we detected the numbers of M1 and M2 macrophages in the border zone of the wound. Then we performed Western-blotting and RT-PCR to investigate the PPAR-γ protein and RNA expression in the wound tissue. And Co-IP was performed to check whether E2F1 interaction with PPAR-γ.
RESULTS: In the border zone of the wound, E2F1-/- mice had more M2 macrophages and less M1 macrophages at day 7 post-surgery. Surprisingly, at day 2, the M2 macrophages were also remarkably increased in the E2F1-/- mice, which suggests a certain degree of transformation amongst the M1 and M2 phenotypes on the 2nd day. We know that PPAR-γ plays a key role in the M1-M2 switch. However, whether E2F1 interacts with PPAR-γ during the wound healing process is not known. We performed Co-IP and found that E2F1 indeed interacts with PPAR-γ. Western-blotting and RT-PCR showed higher expression of PPAR-γ in the E2F1-/- mice as compared to that in the WT mice.
CONCLUSION: E2F1 may repress PPAR-γ expression to affect M1-M2 macrophage switch that prevents skin wound healing.


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