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免疫刺激RNA对博来霉素或脂多糖诱导的小鼠模型中纤维化发展的影响。

Effect of immunostimulatory RNA on the fibrosis development in Bleomycin- or LPS-induced mouse models.

作者信息

Sen'kova Aleksandra V, Bishani Ali, Savin Innokenty A, Zenkova Marina A, Chernolovskaya Elena L

机构信息

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Acad. Lavrentiev Ave. 8, 630090, Novosibirsk, Russia.

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Acad. Lavrentiev Ave. 8, 630090, Novosibirsk, Russia; Faculty of Natural Sciences, Novosibirsk State University, Pirogova Str., 1, 630090, Novosibirsk, Russia.

出版信息

Biochimie. 2025 Feb;229:9-18. doi: 10.1016/j.biochi.2024.09.016. Epub 2024 Oct 1.

Abstract

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

摘要

此前,我们描述了一种具有3'-三核苷酸突出端的19个碱基对的双链RNA,其作为免疫刺激RNA(isRNA)。该分子对癌细胞表现出显著的抗增殖作用,抑制肿瘤生长,并通过诱导细胞因子和干扰素产生引发免疫刺激和抗病毒反应。在本研究中,我们比较了使用不同诱导方案通过博来霉素(BLM)或脂多糖(LPS)在小鼠中引发肺纤维化发展的效率。然后,我们比较了在预防性或治疗性方案中使用的isRNA对选定的BLM和LPS诱导的小鼠模型中纤维化发展的影响,并表明isRNA可用于伴有炎症发展和纤维化形成风险的病理状况,且无不良副作用。isRNA应用的预防性方案有利于预防肺纤维化的发展。

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