Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization
Cold-inducible RNA-binding protein (CIRP) is an intracellular RNA-chaperone and extracellular promoter of inflammation, which is increasingly expressed and released under conditions of hypoxia and cold stress. The functional relevance of CIRP for angiogenesis and regeneration of ischemic muscle tiss...
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MDPI AG
2021-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/4/395 |
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| author | Matthias Kübler Sebastian Beck Silvia Fischer Philipp Götz Konda Kumaraswami Hellen Ishikawa-Ankerhold Manuel Lasch Elisabeth Deindl |
| author_facet | Matthias Kübler Sebastian Beck Silvia Fischer Philipp Götz Konda Kumaraswami Hellen Ishikawa-Ankerhold Manuel Lasch Elisabeth Deindl |
| author_sort | Matthias Kübler |
| collection | DOAJ |
| description | Cold-inducible RNA-binding protein (CIRP) is an intracellular RNA-chaperone and extracellular promoter of inflammation, which is increasingly expressed and released under conditions of hypoxia and cold stress. The functional relevance of CIRP for angiogenesis and regeneration of ischemic muscle tissue has never been investigated and is the topic of the present study. We investigated the role of CIRP employing CIRP deficient mice along with a hindlimb model of ischemia-induced angiogenesis. 1 and 7 days after femoral artery ligation or sham operation, gastrocnemius muscles of CIRP-deficient and wildtype mice were isolated and processed for (immuno-) histological analyses. CIRP deficient mice showed decreased ischemic tissue damage as evidenced by Hematoxylin and Eosin staining, whereas angiogenesis was enhanced as demonstrated by increased capillary/muscle fiber ratio and number of proliferating endothelial (CD31<sup>+</sup>/BrdU<sup>+</sup>) cells on day 7 after surgery. Moreover, CIRP deficiency resulted in a reduction of total leukocyte count (CD45<sup>+</sup>), neutrophils (myeloperoxidase, MPO<sup>+</sup>), neutrophil extracellular traps (NETs) (MPO<sup>+</sup>/CitH3<sup>+</sup>), and inflammatory M1-like polarized macrophages (CD68<sup>+</sup>/MRC1<sup>-</sup>), whereas the number of tissue regenerating M2-like polarized macrophages (CD68<sup>+</sup>/MRC1<sup>-</sup>) was increased in ischemic tissue samples. In summary, we show that the absence of CIRP ameliorates angiogenesis and regeneration of ischemic muscle tissue, most likely by influencing macrophage polarization in direction to regenerative M2-like macrophages. |
| first_indexed | 2024-03-10T12:33:52Z |
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| language | English |
| last_indexed | 2024-03-10T12:33:52Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-76e71e6b9cdb4e23bda2e2d0e6ae60292023-11-21T14:27:16ZengMDPI AGBiomedicines2227-90592021-04-019439510.3390/biomedicines9040395Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage PolarizationMatthias Kübler0Sebastian Beck1Silvia Fischer2Philipp Götz3Konda Kumaraswami4Hellen Ishikawa-Ankerhold5Manuel Lasch6Elisabeth Deindl7Walter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyDepartment of Biochemistry, Faculty of Medicine, Justus Liebig University, 35392 Giessen, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyWalter-Brendel-Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyCold-inducible RNA-binding protein (CIRP) is an intracellular RNA-chaperone and extracellular promoter of inflammation, which is increasingly expressed and released under conditions of hypoxia and cold stress. The functional relevance of CIRP for angiogenesis and regeneration of ischemic muscle tissue has never been investigated and is the topic of the present study. We investigated the role of CIRP employing CIRP deficient mice along with a hindlimb model of ischemia-induced angiogenesis. 1 and 7 days after femoral artery ligation or sham operation, gastrocnemius muscles of CIRP-deficient and wildtype mice were isolated and processed for (immuno-) histological analyses. CIRP deficient mice showed decreased ischemic tissue damage as evidenced by Hematoxylin and Eosin staining, whereas angiogenesis was enhanced as demonstrated by increased capillary/muscle fiber ratio and number of proliferating endothelial (CD31<sup>+</sup>/BrdU<sup>+</sup>) cells on day 7 after surgery. Moreover, CIRP deficiency resulted in a reduction of total leukocyte count (CD45<sup>+</sup>), neutrophils (myeloperoxidase, MPO<sup>+</sup>), neutrophil extracellular traps (NETs) (MPO<sup>+</sup>/CitH3<sup>+</sup>), and inflammatory M1-like polarized macrophages (CD68<sup>+</sup>/MRC1<sup>-</sup>), whereas the number of tissue regenerating M2-like polarized macrophages (CD68<sup>+</sup>/MRC1<sup>-</sup>) was increased in ischemic tissue samples. In summary, we show that the absence of CIRP ameliorates angiogenesis and regeneration of ischemic muscle tissue, most likely by influencing macrophage polarization in direction to regenerative M2-like macrophages.https://www.mdpi.com/2227-9059/9/4/395angiogenesiscold-inducible RNA-binding proteinCIRPCIRBPneutrophil extracellular trapsNETs |
| spellingShingle | Matthias Kübler Sebastian Beck Silvia Fischer Philipp Götz Konda Kumaraswami Hellen Ishikawa-Ankerhold Manuel Lasch Elisabeth Deindl Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization Biomedicines angiogenesis cold-inducible RNA-binding protein CIRP CIRBP neutrophil extracellular traps NETs |
| title | Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization |
| title_full | Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization |
| title_fullStr | Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization |
| title_full_unstemmed | Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization |
| title_short | Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization |
| title_sort | absence of cold inducible rna binding protein cirp promotes angiogenesis and regeneration of ischemic tissue by inducing m2 like macrophage polarization |
| topic | angiogenesis cold-inducible RNA-binding protein CIRP CIRBP neutrophil extracellular traps NETs |
| url | https://www.mdpi.com/2227-9059/9/4/395 |
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