Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases
Abstract Background macrophage-targeting therapy of ischemic disease has made progress in clinic trial. However, the role and underlying mechanism of pro-inflammatory or anti-inflammatory polarized macrophages in modulating ischemic diseases remain incompletely understood. Results here we examine th...
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BMC
2024-12-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-024-01325-2 |
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| author | Haiyi Liu Yonghui Yuan Takerra K. Johnson-Stephenson Chenyang Jing Mingchao Zhang Jun Huang Ke Zen Limin Li Dihan Zhu |
| author_facet | Haiyi Liu Yonghui Yuan Takerra K. Johnson-Stephenson Chenyang Jing Mingchao Zhang Jun Huang Ke Zen Limin Li Dihan Zhu |
| author_sort | Haiyi Liu |
| collection | DOAJ |
| description | Abstract Background macrophage-targeting therapy of ischemic disease has made progress in clinic trial. However, the role and underlying mechanism of pro-inflammatory or anti-inflammatory polarized macrophages in modulating ischemic diseases remain incompletely understood. Results here we examine the effect of pro-inflammatory (LPS) and anti-inflammatory (IL-4) macrophage on ischemic diseases in a mouse ischemic hindlimb and heart model, and identify that signal regulatory protein α (Sirpα) modulates macrophage polarization induced angiogenesis via promoting phagocytosis or activating HIF1α nucleus relocation in macrophages, respectively. More importantly, the therapeutic effect of polarized macrophages is controlled by Sirpα in a time-dependent manner. Downregulation of macrophage Sirpα at the early-stage or upregulation of macrophage Sirpα at the late-stage of ischemic disease enhances the therapeutic effect. In contrast, increasing Sirpα at the early-stage or decreasing it at the late-stage leads to failure of inducing ischemic disease resilience. Mechanistically, we find that signal transducer and activator of transcription 3 and 6 (Stat3 and Stat6) mediate downregulation (pro-inflammatory polarization) or upregulation (anti-inflammatory polarization) of Sirpα, respectively. Conclusion Our results reveal that dynamic regulation of macrophage by Sirpα plays a critical role in alleviating ischemic diseases. |
| format | Article |
| id | doaj-art-0829a8749c0c49f7923c5f2da231d8a7 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-0829a8749c0c49f7923c5f2da231d8a72024-12-22T12:50:24ZengBMCCell & Bioscience2045-37012024-12-0114112110.1186/s13578-024-01325-2Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseasesHaiyi Liu0Yonghui Yuan1Takerra K. Johnson-Stephenson2Chenyang Jing3Mingchao Zhang4Jun Huang5Ke Zen6Limin Li7Dihan Zhu8State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityCardiovascular Research Institute, Morehouse School of MedicineState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityNational Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of MedicineState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University School of Life SciencesState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical UniversityAbstract Background macrophage-targeting therapy of ischemic disease has made progress in clinic trial. However, the role and underlying mechanism of pro-inflammatory or anti-inflammatory polarized macrophages in modulating ischemic diseases remain incompletely understood. Results here we examine the effect of pro-inflammatory (LPS) and anti-inflammatory (IL-4) macrophage on ischemic diseases in a mouse ischemic hindlimb and heart model, and identify that signal regulatory protein α (Sirpα) modulates macrophage polarization induced angiogenesis via promoting phagocytosis or activating HIF1α nucleus relocation in macrophages, respectively. More importantly, the therapeutic effect of polarized macrophages is controlled by Sirpα in a time-dependent manner. Downregulation of macrophage Sirpα at the early-stage or upregulation of macrophage Sirpα at the late-stage of ischemic disease enhances the therapeutic effect. In contrast, increasing Sirpα at the early-stage or decreasing it at the late-stage leads to failure of inducing ischemic disease resilience. Mechanistically, we find that signal transducer and activator of transcription 3 and 6 (Stat3 and Stat6) mediate downregulation (pro-inflammatory polarization) or upregulation (anti-inflammatory polarization) of Sirpα, respectively. Conclusion Our results reveal that dynamic regulation of macrophage by Sirpα plays a critical role in alleviating ischemic diseases.https://doi.org/10.1186/s13578-024-01325-2Macrophage polarizationSirpαIschemic diseasesTime-dependent |
| spellingShingle | Haiyi Liu Yonghui Yuan Takerra K. Johnson-Stephenson Chenyang Jing Mingchao Zhang Jun Huang Ke Zen Limin Li Dihan Zhu Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases Cell & Bioscience Macrophage polarization Sirpα Ischemic diseases Time-dependent |
| title | Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases |
| title_full | Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases |
| title_fullStr | Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases |
| title_full_unstemmed | Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases |
| title_short | Signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases |
| title_sort | signal regulatory protein α dynamically mediates macrophage polarization facilitated alleviation of ischemic diseases |
| topic | Macrophage polarization Sirpα Ischemic diseases Time-dependent |
| url | https://doi.org/10.1186/s13578-024-01325-2 |
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