Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis.
Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis.
复制标题
通过负载 siRNA 的脂质体抑制 Sart1 来调节巨噬细胞极化：一种有前途的肺纤维化治疗策略
作者：
Pan T;Zhou Q;Miao K;Zhang L;Wu G;Yu J;Xu Y;Xiong W;Li Y;Wang Y
特发性肺纤维化（IPF）是一种病因不明的慢性弥漫性间质性肺病，具有致死性结局。尽管在过去几十年中开发了各种IPF策略，但未观察到对IPF预后的显著积极影响。根据目前的模式，巨噬细胞已被认为在IPF发病机制中发挥重要作用。在这里，我们报告了一种基于调节巨噬细胞极化的IPF的潜在纳米医学基因治疗。方法：采用C57 BL/6小鼠建立博莱霉素（BLM）诱导的肺纤维化动物模型，设计Sart 1 siRNA脂质体进行体内实验。实验动物在第0天经气管内给予BLM，并在第14天和第17天用Sart 1 siRNA治疗。在体外实验中，我们进一步研究了Sart 1在巨噬细胞中的功能。结果：脂质体可被动靶向肺纤维化区域，并在巨噬细胞中有效蓄积。Sart 1的抑制siRNA负载的脂质体显着保护小鼠免受BLM诱导的肺损伤和纤维化，这归因于减弱M2巨噬细胞在肺中的浸润。结论：我们的研究为调节巨噬细胞极化提供了有价值的参考，并为临床治疗肺纤维化提供了一种有前途的策略。
Idiopathic pulmonary fibrosis (IPF) is a chronic and diffuse form of interstitial lung disease of unknown etiology with a fatal outcome. Although various strategies for IPF have been developed over the last few decades, no significant positive impact on the prognosis of IPF has been observed. According to the current paradigm, macrophages have been recognized to play a significant role in IPF pathogenesis. Here, we report a potential nanomedicine-based gene therapy for IPF based on regulate macrophage polarization. Method: C57BL/6 mice were obtained and used to establish a bleomycin (BLM)-induced pulmonary fibrosis animal model, and Sart1 siRNA-loaded liposomes were designed for in vivo experiment. The experimental animals were administered BLM intratracheally on day 0 and treated with Sart1 siRNA on days 14 and 17. In the in vitro experiment, we further examined the function of Sart1 in macrophages. Results: Our data indicated that the liposomes could passively target the fibrotic area in the lung and efficiently accumulate in macrophages. The suppression of Sart1 by siRNA-loaded liposomes significantly protected mice against BLM-induced lung injury and fibrosis, which was attributed to attenuated M2 macrophage infiltration in the lung. Conclusion: Our study provides a valuable reference for modulating macrophage polarization and a promising strategy for the treatment of pulmonary fibrosis in clinical settings.
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DOI：
10.1002/reg2.97
发表时间：
2018-03
期刊：
Regeneration (Oxford, England)
影响因子：
--
作者：
Florez-Sampedro L;Song S;Melgert BN
通讯作者：
Melgert BN
将小干扰 RNA 递送至淀粉样斑块附近的神经元，以改善阿尔茨海默病的治疗
影响因子：
14.5
作者：
Guo, Qian;Zheng, Xiaoyao;Jiang, Xinguo
通讯作者：
Jiang, Xinguo
薯蓣皂甙通过促进肺泡巨噬细胞自噬减轻结晶二氧化硅引起的肺部炎症和纤维化
影响因子：
12.4
作者：
Du, Sitong;Li, Chao;Chen, Jie
通讯作者：
Chen, Jie
影响因子：
17.1
作者：
Ramishetti, Srinivas;Kedmi, Ranit;Peer, Dan
通讯作者：
Peer, Dan
影响因子：
10.8
作者：
Chen, Qijing;Gao, Mingzhu;Zhang, Xue-Qing
通讯作者：
Zhang, Xue-Qing