SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway
Yiwen Ma,
Jiateng Hu,
Xingjuan Xue,
Jianmin Gu,
Yuyan Pan,
Jun Yang
Affiliations
Yiwen Ma
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
Jiateng Hu
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Vascular Centre of Shanghai Jiao Tong University, Shanghai, 200011, China
Xingjuan Xue
Department of Thoracic Surgery, Fuqing City Hospital Affiliated to Fujian Medical University, Fuqing City, Fujian Province, 350399, China
Jianmin Gu
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
Yuyan Pan
Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; Corresponding author. Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
Jun Yang
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Corresponding author. Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China.
Macrophages preferentially polarize to the anti-inflammatory M2 subtype in response to alterations in the wound microenvironment. SUMO-specific protease 3 (SENP3), a SUMO-specific protease, has been proven to regulate inflammation in macrophages by deSUMOylating substrate proteins, but its contribution to wound healing is poorly defined. Here, we report that SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing in macrophage-specific SENP3 knockout mice. Notably, it affects wound healing through the suppression of inflammation and promotion of angiogenesis and collagen remodeling. Mechanistically, we identified that SENP3 knockout facilitates M2 polarization through the Smad6/IκB/p65 signaling pathway. SENP3 knockout elevated the expression of Smad6 and IκB. Moreover, Smad6 silencing enhanced the expression of p-p65 and proinflammatory cytokines while inhibiting the level of IκB. Our study revealed the essential role of SENP3 in M2 polarization and wound healing, which offers a theoretical basis for further research and a therapeutic strategy for wound healing.
