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Updated: Jul 30, 2025
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
SENP3 deletion promotes M2 macrophage polarization and accelerates wound healing through smad6/IκB/p65 signaling
Yiwen Ma1, Jiateng Hu2,3, Xingjuan Xue4
1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Abstract:
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.
Insights
Deleting SUMO-specific protease 3 (SENP3) enhances M2 macrophage polarization and accelerates wound healing. This occurs by suppressing inflammation and promoting tissue repair via the Smad6/IκB/p65 pathway.
Area of Science:
- Immunology
- Molecular Biology
- Regenerative Medicine
Background:
- Macrophages play a key role in wound healing, with polarization towards the anti-inflammatory M2 subtype being crucial.
- SUMO-specific protease 3 (SENP3) regulates inflammation in macrophages, but its specific role in wound healing remains unclear.
Purpose of the Study:
- To investigate the role of SENP3 in macrophage polarization and its impact on wound healing.
- To elucidate the underlying molecular mechanisms by which SENP3 influences wound repair.
Main Methods:
- Utilized macrophage-specific SENP3 knockout mice to study wound healing.
- Analyzed macrophage polarization, inflammatory responses, angiogenesis, and collagen remodeling.
- Investigated the involvement of the Smad6/IκB/p65 signaling pathway.
Main Results:
- SENP3 deletion promoted M2 macrophage polarization and accelerated wound healing.
- SENP3 knockout suppressed inflammation and enhanced angiogenesis and collagen remodeling.
- Mechanistically, SENP3 deficiency upregulated Smad6 and IκB, facilitating M2 polarization via the Smad6/IκB/p65 pathway.
Conclusions:
- SENP3 is essential for regulating M2 macrophage polarization and wound healing.
- Targeting SENP3 offers a potential therapeutic strategy for improving wound repair by modulating macrophage function and inflammation.
