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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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-12-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-024-01325-2 |
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| Summary: | 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. |
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| ISSN: | 2045-3701 |