外泌体衍生的 CIRP：炎症性疾病的放大器,Frontiers in Immunology

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外泌体衍生的 CIRP：炎症性疾病的放大器
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2023-02-14 , DOI: 10.3389/fimmu.2023.1066721
Jingrun Han ₁ , Yibo Zhang _{1,

2,

3} , Peng Ge _{1,

2,

3} , Tikam Chand Dakal ₄ , Haiyun Wen _{1,

2,

3} , Shuangfeng Tang ₁ , Yalan Luo _{1,

2,

3} , Qi Yang _{1,

2,

3} , Bianca Hua ₅ , Guixin Zhang ₁ , Hailong Chen _{1,

2,

3} , Caiming Xu _{1,

5}

Affiliation

冷诱导 RNA 结合蛋白 (CIRP) 是一种细胞内应激反应蛋白和一种损伤相关分子模式 (DAMP)，它通过改变其表达和 mRNA 稳定性来响应各种应激刺激。暴露于紫外线 (UV) 光或低温后，CIRP 通过甲基化修饰从细胞核转移到细胞质，并储存在应激颗粒 (SG) 中。在外泌体生物发生过程中，包括通过内吞作用从细胞膜形成内体，CIRP 也与 DNA、RNA 和其他蛋白质一起被包装在内体内。随后，内体膜向内出芽后形成腔内囊泡 (ILV)，将内体转变为多囊泡体 (MVB)。最后，MVB 与细胞膜融合形成外泌体。因此，CIRP 也可以作为细胞外 CIRP (eCIRP) 通过溶酶体途径分泌出细胞。细胞外 CIRP (eCIRP) 通过释放外泌体参与多种疾病，包括败血症、缺血再灌注损伤、肺损伤和神经炎症。此外，CIRP 与 TLR4、TREM-1 和 IL-6R 相互作用，因此参与触发免疫和炎症反应。因此，eCIRP 已被研究作为疾病治疗的潜在新靶点。C23 和 M3 是反对 eCIRP 与其受体结合的多肽，对多种炎症性疾病有益。一些天然分子如木犀草素和大黄素也可以拮抗 CIRP，CIRP 在炎症反应中发挥类似于 C23 的作用，抑制巨噬细胞介导的炎症。

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Exosome-derived CIRP: An amplifier of inflammatory diseases

Cold-inducible RNA-binding protein (CIRP) is an intracellular stress-response protein and a type of damage-associated molecular pattern (DAMP) that responds to various stress stimulus by altering its expression and mRNA stability. Upon exposure to ultraviolet (UV) light or low temperature, CIRP get translocated from the nucleus to the cytoplasm through methylation modification and stored in stress granules (SG). During exosome biogenesis, which involves formation of endosomes from the cell membrane through endocytosis, CIRP also gets packaged within the endosomes along with DNA, and RNA and other proteins. Subsequently, intraluminal vesicles (ILVs) are formed following the inward budding of the endosomal membrane, turning the endosomes into multi-vesicle bodies (MVBs). Finally, the MVBs fuse with the cell membrane to form exosomes. As a result, CIRP can also be secreted out of cells through the lysosomal pathway as Extracellular CIRP (eCIRP). Extracellular CIRP (eCIRP) is implicated in various conditions, including sepsis, ischemia-reperfusion damage, lung injury, and neuroinflammation, through the release of exosomes. In addition, CIRP interacts with TLR4, TREM-1, and IL-6R, and therefore are involved in triggering immune and inflammatory responses. Accordingly, eCIRP has been studied as potential novel targets for disease therapy. C23 and M3, polypeptides that oppose eCIRP binding to its receptors, are beneficial in numerous inflammatory illnesses. Some natural molecules such as Luteolin and Emodin can also antagonize CIRP, which play roles similar to C23 in inflammatory responses and inhibit macrophage-mediated inflammation. This review aims to provide a better understanding on CIRP translocation and secretion from the nucleus to the extracellular space and the mechanisms and inhibitory roles of eCIRP in diverse inflammatory illnesses.

更新日期：2023-02-14

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