MicroRNA-206 antagomiR‒enriched extracellular vesicles attenuate lung ischemia‒reperfusion injury through CXCL1 regulation in alveolar epithelial cells.
MicroRNA-206 antagomiR‒enriched extracellular vesicles attenuate lung ischemia‒reperfusion injury through CXCL1 regulation in alveolar epithelial cells.
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DOI：
10.1016/j.healun.2020.09.012
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Sharma AK
中科院分区：
文献类型：
--
作者：
Cai J;Gehrau R;Tu Z;Leroy V;Su G;Shang J;Mas VR;Emtiazjoo A;Pelaez A;Atkinson C;Machuca T;Upchurch GR Jr;Sharma AK
我们的假设是，间充质干细胞（MSC）衍生的细胞外囊泡（EV）的免疫调节能力可以通过特定的microRNA增强，以有效地减轻移植后肺缺血再灌注（IR）损伤。在肺移植后第0天和第1天分析患者的BAL液中miR-206的表达。使用左肺门结扎模型在C57 BL/6小鼠中评估肺IR损伤，用或不用EV或富含EkomiR-206的EV治疗。小鼠肺组织用于microRNA微阵列杂交分析，并评估细胞因子表达、肺损伤和水肿。采用循环死亡后供体和小鼠原位肺移植模型评价富集EV对肺IR损伤的保护作用。体外研究分析了与EV共培养后的II型上皮细胞活化。在肺移植后患者中，与第0天相比，在第1天的BAL液中观察到miR-206的显著上调，并且与假手术相比，在IR损伤后的鼠肺中观察到miR-206的显著上调。在鼠肺IR损伤后，与单独用EV治疗相比，用富含EkomiR-206的EV治疗减轻了肺功能障碍、损伤和水肿。富集EV减少了小鼠原位肺移植后的肺损伤和中性粒细胞浸润，并改善了同种异体肺移植物氧合。在体内和体外IR损伤模型中，富集EV显著降低促炎细胞因子，特别是上皮细胞依赖性CXCL 1表达。EV可用作仿生纳米载体，通过使其富含EkomiR-206来进行保护性免疫调节，以减轻IR损伤后肺中的上皮细胞活化和中性粒细胞浸润。
Our hypothesis is that the immunomodulatory capacities of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) can be enhanced by specific microRNAs to effectively attenuate post-transplant lung ischemia-reperfusion (IR) injury. Expression of miR-206 was analyzed in BAL fluid of patients on days 0 and 1 post-lung transplantation. Lung IR injury was evaluated in C57BL/6 mice using a left lung hilar-ligation model with or without treatment with EVs or antagomiR-206 enriched EVs. Murine lung tissue was used for microRNA microarray hybridization analysis, and cytokine expression, lung injury and edema were evaluated. A donation after circulatory death and murine orthotopic lung transplantation model was used to evaluate the protection by enriched EVs against lung IR injury. In vitro studies analyzed type II epithelial cell activation after co-cultures with EVs. A significant upregulation of miR-206 was observed in BAL fluid on day 1 compared to day 0 in post-lung transplant patients, and in murine lungs after IR injury compared to sham. Treatment with antagomiR-206-enriched EVs attenuated lung dysfunction, injury and edema compared to treatment with EVs alone after murine lung IR injury. Enriched EVs reduced lung injury and neutrophil infiltration as well as improved allograft oxygenation after murine orthotopic lung transplantation. Enriched EVs significantly decreased proinflammatory cytokines, especially epithelial cell-dependent CXCL1 expression, in the in vivo and in vitro IR injury models. EVs can be used as biomimetic nanovehicles for protective immunomodulation by enriching them with antagomiR-206, to mitigate epithelial cell activation and neutrophil infiltration in lungs after IR injury.
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影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
3.7
作者：
Haas JD;Nistala K;Petermann F;Saran N;Chennupati V;Schmitz S;Korn T;Wedderburn LR;Förster R;Krueger A;Prinz I
通讯作者：
Prinz I
影响因子：
2.3
作者：
Gharib, Sina A.;Edelman, Jeffery D.;Chen, Peter
通讯作者：
Chen, Peter
DOI：
10.1152/ajplung.00205.2013
发表时间：
2014-01-01
影响因子：
4.9
作者：
Sharma, Ashish K.;Mulloy, Daniel P.;Laubach, Victor E.
通讯作者：
Laubach, Victor E.
DOI：
10.1016/j.jtcvs.2010.09.009
发表时间：
2011-01-01
影响因子：
6
作者：
Kreisel, Daniel;Krupnick, Alexander S.;Patterson, G. Alexander
通讯作者：
Patterson, G. Alexander