IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A
Abstract Keloid is benign skin tumor, and their curing is relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis of keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs ferroptosis through inhibiting...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-024-02257-z |
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| author | Xiuxia Wang Yating Yang Xianyu Zhou Shun Yu Xusong Luo Lin Lu Zhen Gao Jun Yang |
| author_facet | Xiuxia Wang Yating Yang Xianyu Zhou Shun Yu Xusong Luo Lin Lu Zhen Gao Jun Yang |
| author_sort | Xiuxia Wang |
| collection | DOAJ |
| description | Abstract Keloid is benign skin tumor, and their curing is relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis of keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs ferroptosis through inhibiting SPOC domain-containing protein 1 (SPOCD1), serving as a mode of action for CD8+T cell (CTL)-mediated keloid killing. Mechanistically, keloid IFNγ deficiency in combination with reduced DNMT3A increase the expression of SPOCD1, thereby promoting KFs’ proliferation and inhibiting its ferroptosis. Moreover, keloid SPOCD1 deficiency attenuates KFs progression and extracellular matrix (ECM) deposition. Reducing IFNγ and SPOCD1 simultaneously can increase the positive rate of reactive oxygen species (ROS) and promote mitochondrial shrinkage. Ex-vivo explant keloid culture has also confirmed that the reduction of SPOCD1 helps to reduce the proliferation rate of KFs, inhibit the angiogenesis of keloid scars, and thus inhibit keloid formation. Thus, IFNγ signaling paired with SPOCD1 is a natural keloid ferroptosis promoting mechanism and a mode of action of CTLs. Targeting SPOCD1 pathway is a potential anti-keloid approach. |
| format | Article |
| id | doaj-art-e2266574cabd4e7fad7587eaf37425d2 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-e2266574cabd4e7fad7587eaf37425d22025-01-19T12:10:29ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111210.1038/s41420-024-02257-zIFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3AXiuxia Wang0Yating Yang1Xianyu Zhou2Shun Yu3Xusong Luo4Lin Lu5Zhen Gao6Jun Yang7Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineThe Affiliated Hospital of Jiangnan UniversityDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of MedicineAbstract Keloid is benign skin tumor, and their curing is relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis of keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs ferroptosis through inhibiting SPOC domain-containing protein 1 (SPOCD1), serving as a mode of action for CD8+T cell (CTL)-mediated keloid killing. Mechanistically, keloid IFNγ deficiency in combination with reduced DNMT3A increase the expression of SPOCD1, thereby promoting KFs’ proliferation and inhibiting its ferroptosis. Moreover, keloid SPOCD1 deficiency attenuates KFs progression and extracellular matrix (ECM) deposition. Reducing IFNγ and SPOCD1 simultaneously can increase the positive rate of reactive oxygen species (ROS) and promote mitochondrial shrinkage. Ex-vivo explant keloid culture has also confirmed that the reduction of SPOCD1 helps to reduce the proliferation rate of KFs, inhibit the angiogenesis of keloid scars, and thus inhibit keloid formation. Thus, IFNγ signaling paired with SPOCD1 is a natural keloid ferroptosis promoting mechanism and a mode of action of CTLs. Targeting SPOCD1 pathway is a potential anti-keloid approach.https://doi.org/10.1038/s41420-024-02257-z |
| spellingShingle | Xiuxia Wang Yating Yang Xianyu Zhou Shun Yu Xusong Luo Lin Lu Zhen Gao Jun Yang IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A Cell Death Discovery |
| title | IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A |
| title_full | IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A |
| title_fullStr | IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A |
| title_full_unstemmed | IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A |
| title_short | IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A |
| title_sort | ifnγ regulates ferroptosis in kfs by inhibiting the expression of spocd1 through dnmt3a |
| url | https://doi.org/10.1038/s41420-024-02257-z |
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