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脂肪间充质干细胞来源的外泌体递送的 miR-181a-5p 通过靶向 STAT3 信号通路缓解肺炎感染诱导的肺损伤。

MiR-181a-5p Delivered by Adipose-Derived Mesenchymal Stem Cell Exosomes Alleviates pneumonia Infection-Induced Lung Injury by Targeting STAT3 Signaling.

机构信息

Department of Laboratory Medicine, Wuxi Second People's Hospital Affiliated to Nanjing Medical University, Wuxi City, 214000 Jiangsu Province, China.

Department of Laboratory Medicine, Taizhou Second People's Hospital, Taizhou City, 225411 Jiangsu Province, China.

出版信息

Mediators Inflamm. 2022 Dec 14;2022:5188895. doi: 10.1155/2022/5188895. eCollection 2022.

Abstract

BACKGROUND

() is a leading cause of gram-negative pneumonia, which requires effective treatment. Adipose-derived mesenchymal stem cell- (ADSC-) derived exosomal microRNAs (miRNAs) have presented the inhibitory effect of multiple diseases. However, the function of ADSC-derived exosomal miRNAs in remains unclear.

AIM

In this study, we aimed to explore the effect of ADSC-derived exosomal miR-181-5p on infection-induced lung injury.

METHODS

C57BL/6 mouse model was established by infection of . ADSCs and exosomes were extracted and characterized in vitro. The translocation of ADSC-derived exosomes to bone marrow-derived macrophages (BMDMs) was detected. The level of miR-181a-5p was detected by real-time PCR. The secretion of inflammatory factors was determined by ELISA. The interaction between miR-181a-5p with STAT3 was identified.

RESULTS

We successfully isolated the ADSCs that express positive markers CD90 and CD105 rather than CD31 and CD45. The exosomal miR-181a-5p secreted by ADSCs were internalized by BMDM and infection stimulated the miR-181a-5p level in bronchoalveolar lavage fluid (BALF) and BMDM. ADSC-derived exosomal miR-181a-5p repressed pulmonary outgrowth and dissemination of infection in mice, repressed cellular infiltration in lung tissue, and attenuated the inflammasome activity and the levels of IL-1 and IL-18 in the lung. Mechanically, miR-181a-5p was able to inhibit STAT3 expression at posttranscriptional levels and repressed Nlrp3 and Asc expression in BMDM.

CONCLUSION

Consequently, we concluded that ADSC-derived exosomal miR-181a-5p alleviated pneumonia infection-induced lung injury by targeting STAT3 signaling. ADSC-derived exosomal miR-181a-5p may serve as a potential candidate for the treatment of pneumonia infection-induced lung injury.

摘要

背景

()是革兰氏阴性肺炎的主要病因,需要有效的治疗。脂肪间充质干细胞衍生的外泌体 microRNAs (miRNAs) 对多种疾病具有抑制作用。然而,ADSC 衍生的外泌体 miRNAs 在中的功能尚不清楚。

目的

本研究旨在探讨 ADSC 衍生的外泌体 miR-181-5p 对 感染诱导的肺损伤的影响。

方法

通过感染 建立 C57BL/6 小鼠模型。体外提取和鉴定 ADSC 和外泌体。检测 ADSC 衍生的外泌体向骨髓来源的巨噬细胞 (BMDM) 的转位。实时 PCR 检测 miR-181a-5p 水平。ELISA 测定炎症因子的分泌。鉴定 miR-181a-5p 与 STAT3 的相互作用。

结果

我们成功分离出表达阳性标志物 CD90 和 CD105 而非 CD31 和 CD45 的 ADSC。ADSC 分泌的外泌体 miR-181a-5p 被 BMDM 内化,而 感染刺激了支气管肺泡灌洗液 (BALF) 和 BMDM 中 miR-181a-5p 的水平。ADSC 衍生的外泌体 miR-181a-5p 抑制了小鼠 感染的肺部生长和扩散,抑制了肺组织中的细胞浸润,并减弱了炎症小体的活性和肺中的 IL-1 和 IL-18 水平。机制上,miR-181a-5p 能够在转录后水平抑制 STAT3 的表达,并抑制 BMDM 中的 Nlrp3 和 Asc 表达。

结论

因此,我们得出结论,ADSC 衍生的外泌体 miR-181a-5p 通过靶向 STAT3 信号通路减轻 肺炎感染引起的肺损伤。ADSC 衍生的外泌体 miR-181a-5p 可能成为治疗 肺炎感染引起的肺损伤的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b6/9771653/1eb8166b52dd/MI2022-5188895.001.jpg

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