Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Radiation-Induced Lung InjuryviamiRNA-214-3p

被引：88

作者：

Lei, Xudan ^{[1
,2
]}

He, Ningning ^{[3
]}

Zhu, Lihong ^{[4
]}

Zhou, Manqian ^{[5
]}

Zhang, Kaiyue ^{[1
]}

Wang, Chen ^{[1
]}

Huang, Haoyan ^{[1
]}

Chen, Shang ^{[1
]}

Li, Yuhao ^{[1
]}

Liu, Qiang ^{[3
]}

Han, Zhibo ^{[6
,7
]}

Guo, Zhikun ^{[8
]}

Han, Zhongchao ^{[6
,7
]}

Li, Zongjin ^{[1
,2
,9
]}

机构：

[1] Nankai Univ, Sch Med, Lab Mol Imaging & Stem Cell Therapy, 94 Weijin Rd, Tianjin 300071, Peoples R China

[2] Nankai Univ, Key Lab Bioact Mat, Minist Educ, Coll Life Sci, Tianjin, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, Tianjin Key Lab Radiat Med & Mol Nucl Med, Dept Radiobiol, Inst Radiat Med, Tianjin, Peoples R China

[4] Capital Med Univ, Beijing Obstet & Gynecol Hosp, Dept Gynecol Oncol, Beijing 100026, Peoples R China

[5] Tianjin Union Med Ctr, Dept Radiat Oncol, Tianjin, Peoples R China

[6] AmCellGene Co Ltd, Tianjin Key Lab Engn Technol Cell Pharmaceut, Natl Engn Res Ctr Cell Prod, Tianjin, Peoples R China

[7] Jiangxi Engn Res Ctr Stem Cell, Shangrao, Peoples R China

[8] Xinxiang Med Univ, Henan Key Lab Med Tissue Regenerat, Xinxiang, Henan, Peoples R China

[9] Chinese Peoples Liberat Army Gen Hosp, State Key Lab Kidney Dis, Beijing, Peoples R China

来源：

ANTIOXIDANTS & REDOX SIGNALING | 2021年 / 35卷 / 11期

基金：

中国国家自然科学基金;

关键词：

radiation-induced lung injury; mesenchymal stem cell; extracellular vesicles; miR-214-3p; ataxia telangiectasia mutated (ATM); STROMAL CELLS; ENDOTHELIAL-CELLS; IONIZING-RADIATION; SENESCENCE; EXOSOMES; MECHANISMS; THERAPY; TARGET; INJURY; ATM;

D O I：

10.1089/ars.2019.7965

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aims:Radiotherapy is an effective treatment for thoracic malignancies, but it can cause pulmonary injury and may lead to respiratory failure in a subset of patients. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are now recognized as a new candidate for cell-free treatment of lung diseases. Here, we investigated whether MSC-derived EVs (MSC-EVs) could ameliorate radiation-induced lung injury. Results:We exposed mice to thoracic radiation with a total dose of 15 Gy and assessed the protective effects of MSC-EVs on endothelial cells damage, vascular permeability, inflammation, and fibrosis. We found that MSC-EVs attenuated radiation-induced lung vascular damage, inflammation, and fibrosis. Moreover, MSC-EVs reduced the levels of radiation-induced DNA damage by downregulating ATM/P53/P21 signaling. Our results confirmed that the downregulation of ataxia telangiectasia mutated (ATM) was regulated by miR-214-3p, which was enriched in MSC-EVs. Further analysis demonstrated that MSC-EVs inhibited the senescence-associated secretory phenotype development and attenuated the radiation-induced injury of endothelial cells. Innovation and Conclusion:Our study reveals that MSC-EVs can reduce pulmonary radiation injury through transferring miR-214-3p, providing new avenues to minimize lung injury from radiation therapy.

引用

页码：849 / 862

页数：14

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