期刊
BIOMEDICINES
卷 9, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines9040395
关键词
angiogenesis; cold-inducible RNA-binding protein; CIRP; CIRBP; neutrophil extracellular traps; NETs; macrophage polarization; inflammation; tissue regeneration; ischemia
资金
- Ludwig-Maximilians-Universitat, Munich, Germany
- DFG [SFB 914]
The study shows that the absence of CIRP can improve angiogenesis and regeneration of ischemic muscle tissue, likely by influencing macrophage polarization towards regenerative M2-like macrophages.
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(+)/BrdU(+)) cells on day 7 after surgery. Moreover, CIRP deficiency resulted in a reduction of total leukocyte count (CD45(+)), neutrophils (myeloperoxidase, MPO+), neutrophil extracellular traps (NETs) (MPO+/CitH3(+)), and inflammatory M1-like polarized macrophages (CD68(+)/MRC1(-)), whereas the number of tissue regenerating M2-like polarized macrophages (CD68(+)/MRC1(-)) 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据