Ma Yiwen, Hu Jiateng, Xue Xingjuan, Gu Jianmin, Pan Yuyan, Yang Jun
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Heliyon. 2023 Apr 25;9(5):e15584. doi: 10.1016/j.heliyon.2023.e15584. eCollection 2023 May.
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.
巨噬细胞会优先响应伤口微环境的变化而极化为抗炎性M2亚型。SUMO特异性蛋白酶3（SENP3）是一种SUMO特异性蛋白酶，已被证明可通过使底物蛋白去SUMO化来调节巨噬细胞中的炎症，但它对伤口愈合的作用尚不清楚。在此，我们报告在巨噬细胞特异性SENP3基因敲除小鼠中，SENP3缺失促进M2巨噬细胞极化并加速伤口愈合。值得注意的是，它通过抑制炎症、促进血管生成和胶原蛋白重塑来影响伤口愈合。从机制上讲，我们发现SENP3基因敲除通过Smad6/IκB/p65信号通路促进M2极化。SENP3基因敲除提高了Smad6和IκB的表达。此外，Smad6沉默增强了p-p65和促炎细胞因子的表达，同时抑制了IκB的水平。我们的研究揭示了SENP3在M2极化和伤口愈合中的重要作用，为进一步研究提供了理论基础，并为伤口愈合提供了一种治疗策略。
