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SR-717，一种非核苷酸STING激动剂，以白细胞介素-6依赖的方式表现出抗辐射活性。

SR-717, a Non-Nucleotide STING Agonist, Displayed Anti-Radiation Activity in a IL-6 Dependent Manner.

作者信息

Fang Duo, Duan Wanli, Zhai Xuanlu, Zhang Liao, Fang Jiayan, Jiang Keer, Zhao Jianpeng, Fu Yue, Fang Lan, Pei Lu, Liu Cong, Du Jicong, Cai Jianming, Gao Fu

机构信息

Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, Shanghai, China.

School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.

出版信息

FASEB J. 2025 Jun 15;39(11):e70644. doi: 10.1096/fj.202403127R.

DOI:10.1096/fj.202403127R
PMID:40448435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12125615/
Abstract

Ionizing radiation (IR) induced damages are common complications of radiotherapy for tumors, severely limiting the intensity and therapeutic efficacy of the radiotherapy program. Emerging data indicated that the cGAS-STING pathway has paradoxical effects on IR-induced damage. SR-717, as a non-nucleotide, small-molecule stimulator of interferon genes (STING) agonist, has been proven that it could activate the STING signaling pathway. In this work, we try to explore the radioprotection of the STING signaling pathway and figure out whether SR-717 could be a potential intestinal radioprotective agent. C57BL/6 mice were intraperitoneally treated with SR-717 or normal saline (NS). By analyzing the survival rate, body weight, and the number of peripheral blood cells after IR exposure, we found that SR-717 improved the survival rate and body weight of mice, protected the intestine from IR-induced damage as well as hematopoietic damage, and promoted the regeneration of intestinal stem cells (ISCs). Cell viability and apoptosis after irradiation were detected after stimulation of MODE-K cells with SR-717 or PBS. We found that SR-717 increased cell viability and inhibited apoptosis in vitro. The mechanism of SR-717 in intestinal radiation protection was investigated by RNA-seq. The results of RNA-seq and qRT-PCR suggested that SR-717 significantly activated the immune system via the STING-IL-6 signaling pathway. In addition, we discussed the role of TLR2 in SR-717-mediated anti-radiation activity, and TLR2 deletion significantly reversed the radioprotective effects of SR717. In conclusion, we proved STING signaling activation displayed anti-radiation activity and found SR-717 displayed anti-radiation activity via the STING-IL-6 signaling pathway, suggesting SR-717 could be a potential intestinal radioprotective agent.

摘要

电离辐射（IR）诱导的损伤是肿瘤放射治疗的常见并发症，严重限制了放射治疗方案的强度和疗效。新出现的数据表明，cGAS-STING通路对IR诱导的损伤具有矛盾的影响。SR-717作为一种非核苷酸、小分子干扰素基因（STING）激动剂刺激物，已被证明可以激活STING信号通路。在这项研究中，我们试图探索STING信号通路的辐射防护作用，并弄清楚SR-717是否可能是一种潜在的肠道辐射防护剂。对C57BL/6小鼠腹腔注射SR-717或生理盐水（NS）。通过分析IR照射后小鼠的存活率、体重和外周血细胞数量，我们发现SR-717提高了小鼠的存活率和体重，保护肠道免受IR诱导的损伤以及造血损伤，并促进肠道干细胞（ISC）的再生。用SR-717或PBS刺激MODE-K细胞后，检测照射后的细胞活力和凋亡情况。我们发现SR-717在体外增加了细胞活力并抑制了凋亡。通过RNA测序研究SR-717在肠道辐射防护中的机制。RNA测序和qRT-PCR结果表明，SR-717通过STING-IL-6信号通路显著激活免疫系统。此外，我们讨论了TLR2在SR-717介导的抗辐射活性中的作用，TLR2缺失显著逆转了SR717的辐射防护作用。总之，我们证明了STING信号激活具有抗辐射活性，并发现SR-717通过STING-IL-6信号通路发挥抗辐射活性，表明SR-717可能是一种潜在的肠道辐射防护剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/242f8f720bfb/FSB2-39-e70644-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/668998e8832e/FSB2-39-e70644-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/2527dd511ed3/FSB2-39-e70644-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/9d080d6fd8fe/FSB2-39-e70644-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/f66abed4a2ae/FSB2-39-e70644-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/408594483bee/FSB2-39-e70644-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/242f8f720bfb/FSB2-39-e70644-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/668998e8832e/FSB2-39-e70644-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/2527dd511ed3/FSB2-39-e70644-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/9d080d6fd8fe/FSB2-39-e70644-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/f66abed4a2ae/FSB2-39-e70644-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/408594483bee/FSB2-39-e70644-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6edf/12125615/242f8f720bfb/FSB2-39-e70644-g002.jpg

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本文引用的文献

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Int Immunopharmacol. 2024 Sep 10;138:112614. doi: 10.1016/j.intimp.2024.112614. Epub 2024 Jul 6.
2
Research progress of cGAS-STING signaling pathway in intestinal diseases.cGAS-STING 信号通路在肠道疾病中的研究进展。
Int Immunopharmacol. 2024 Jun 30;135:112271. doi: 10.1016/j.intimp.2024.112271. Epub 2024 May 18.
3
Intestinal stem cells: guardians of homeostasis in health and aging amid environmental challenges.
肠道干细胞：在环境挑战中维护健康和衰老过程中的体内平衡的守护者。
Exp Mol Med. 2024 Mar;56(3):495-500. doi: 10.1038/s12276-024-01179-1. Epub 2024 Mar 1.
4
Nuclear localization of STING1 competes with canonical signaling to activate AHR for commensal and intestinal homeostasis.STING1 的核定位与经典信号通路竞争，以激活 AHR 促进共生和肠道稳态。
Immunity. 2023 Dec 12;56(12):2736-2754.e8. doi: 10.1016/j.immuni.2023.11.001. Epub 2023 Nov 27.
5
STING is a cell-intrinsic metabolic checkpoint restricting aerobic glycolysis by targeting HK2.STING 是一种细胞内代谢检查点，通过靶向 HK2 限制有氧糖酵解。
Nat Cell Biol. 2023 Aug;25(8):1208-1222. doi: 10.1038/s41556-023-01185-x. Epub 2023 Jul 13.
6
STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma.STING 抑制肺腺癌休眠转移的再激活。
Nature. 2023 Apr;616(7958):806-813. doi: 10.1038/s41586-023-05880-5. Epub 2023 Mar 29.
7
Cellular functions of cGAS-STING signaling.cGAS-STING 信号转导的细胞功能。
Trends Cell Biol. 2023 Aug;33(8):630-648. doi: 10.1016/j.tcb.2022.11.001. Epub 2022 Nov 24.
8
Zymosan-A promotes the regeneration of intestinal stem cells by upregulating ASCL2.酵母聚糖 A 通过上调 ASCL2 促进肠干细胞的再生。
Cell Death Dis. 2022 Oct 20;13(10):884. doi: 10.1038/s41419-022-05301-x.
9
Modeling Intestinal Stem Cell Function with Organoids.类器官技术在肠道干细胞功能研究中的应用。
Int J Mol Sci. 2021 Oct 9;22(20):10912. doi: 10.3390/ijms222010912.
10
Interferon b drives intestinal regeneration after radiation.干扰素β可促进辐射后的肠道再生。
Sci Adv. 2021 Oct 8;7(41):eabi5253. doi: 10.1126/sciadv.abi5253. Epub 2021 Oct 6.