SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway
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 contribut...
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Elsevier
2023-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023027913 |
| _version_ | 1797815644610101248 |
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| author | Yiwen Ma Jiateng Hu Xingjuan Xue Jianmin Gu Yuyan Pan Jun Yang |
| author_facet | Yiwen Ma Jiateng Hu Xingjuan Xue Jianmin Gu Yuyan Pan Jun Yang |
| author_sort | Yiwen Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T08:26:55Z |
| format | Article |
| id | doaj.art-91768281302d405fab6c0d2d58caf948 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T08:26:55Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj.art-91768281302d405fab6c0d2d58caf9482023-05-31T04:44:49ZengElsevierHeliyon2405-84402023-05-0195e15584SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathwayYiwen Ma0Jiateng Hu1Xingjuan Xue2Jianmin Gu3Yuyan Pan4Jun Yang5Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, ChinaDepartment 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, ChinaDepartment of Thoracic Surgery, Fuqing City Hospital Affiliated to Fujian Medical University, Fuqing City, Fujian Province, 350399, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, ChinaDepartment 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.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.http://www.sciencedirect.com/science/article/pii/S2405844023027913SENP3Macrophage polarizationInflammatory responseWound healingSmad6/IκB/p65 signaling pathway |
| spellingShingle | Yiwen Ma Jiateng Hu Xingjuan Xue Jianmin Gu Yuyan Pan Jun Yang SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway Heliyon SENP3 Macrophage polarization Inflammatory response Wound healing Smad6/IκB/p65 signaling pathway |
| title | SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway |
| title_full | SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway |
| title_fullStr | SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway |
| title_full_unstemmed | SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway |
| title_short | SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling pathway |
| title_sort | senp3 deletion promotes m2 macrophage polarization and accelerates wound healing through smad6 iκb p65 signaling pathway |
| topic | SENP3 Macrophage polarization Inflammatory response Wound healing Smad6/IκB/p65 signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023027913 |
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