Hematoma-derived exosomes of chronic subdural hematoma promote abnormal angiogenesis and inhibit hematoma absorption through miR-144-5p

被引：13

作者：

Gao, Chuang ^{[1
,2
]}

Gong, Zhitao ^{[1
,2
]}

Wang, Dong ^{[1
,2
]}

Huang, Jinhao ^{[1
,2
]}

Qian, Yu ^{[1
,2
]}

Nie, Meng ^{[1
,2
]}

Jiang, Weiwei ^{[1
,2
]}

Liu, Xuanhui ^{[1
,2
]}

Luo, Hongliang ^{[1
,2
]}

Yuan, Jiangyuan ^{[1
,2
]}

Xiang, Tangtang ^{[1
,2
]}

An, Shuo ^{[1
,2
]}

Quan, Wei ^{[1
,2
]}

Wei, Huijie ^{[1
,2
]}

Zhang, Jianning ^{[1
,2
]}

Jiang, Rongcai ^{[1
,2
]}

机构：

[1] Tianjin Med Univ, Gen Hosp, Dept Neurosurg, Tianjin, Peoples R China

[2] Minist Educ, Key Lab Postneuroinjury Neurorepair & Regenerat C, Tianjin Neurol Inst, Tianjin, Peoples R China

来源：

AGING-US | 2019年 / 11卷 / 24期

基金：

中国国家自然科学基金;

关键词：

chronic subdural hematoma; exosomes; miR-144-5p; angiogenesis; hematoma absorption; ENDOTHELIAL GROWTH-FACTOR; EXPRESSION; DRAINAGE; CAPSULE; RNA;

D O I：

10.18632/aging.102550

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Exosomes are small (30-150 nm diameter) lipid bilayer-enclosed vesicles found in all bodily fluids. We investigated whether exosomes play a role in chronic subdural hematoma (CSDH). Exosomes were identified and characterized using transmission electron microscopy and NanoSight particle tracking. The functions of hematoma-derived exosomes were evaluated in a rat model of acute subdural hematoma (SDH). The hematoma-derived exosomes inhibited hematoma absorption and exacerbated neurological deficits in SDH rats. We examined the effects of the exosomes on angiogenesis and cell permeability in human umbilical vein endothelial cells (HUVECs). Co-culture of exosomes with HUVECs revealed that the hematoma-derived exosomes were taken-in by the HUVECs, resulting in enhanced tube formation and vascular permeability. Additionally, there was a concomitant increase in ANG-2 expression and decrease in ANG-1 expression. Exosomes were enriched with microRNAs including miR-144-5p, which they could deliver to HUVECs to promote angiogenesis and increase membrane permeability. Overexpression of miR-144-5p in HUVECs and in SDH rats promoted abnormal angiogenesis and reduced hematoma absorption, which mimicked the effects of the hematoma-derived exosomes both in vitro and in vivo. Thus, hematoma-derived exosomes promote abnormal angiogenesis with high permeability and inhibit hematoma absorption through miR-144-5p in CSDH.

引用

页码：12147 / 12164

页数：18

共 41 条

[1] Actual and projected incidence rates for chronic subdural hematomas in United States Veterans Administration and civilian populations [J].

Balser, David ;

Farooq, Sameer ;

Mehmood, Talha ;

Reyes, Marleen ;

Samadani, Uzma .

JOURNAL OF NEUROSURGERY, 2015, 123 (05) :1209-1215

[2]

Chang CW, 2015, ANTICANCER RES, V35, P3969

[3]

De Rossi Giulia, 2013, F1000Res, V2, P270, DOI 10.12688/f1000research.2-270.v1

[4] The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction [J].

Elbaz, A ;

Poirier, O ;

Canaple, S ;

Chédru, F ;

Cambien, F ;

Amarenco, P .

BLOOD, 2000, 95 (02) :586-591

[5] Angiopoietins in angiogenesis [J].

Fagiani, Ernesta ;

Christofori, Gerhard .

CANCER LETTERS, 2013, 328 (01) :18-26

[6] Exosomes as Novel Regulators of Adult Neurogenic Niches [J].

Federico Batiz, Luis ;

Castro, Maite A. ;

Burgos, Patricia V. ;

Velasquez, Zahady D. ;

Munoz, Rosa I. ;

Lafourcade, Carlos A. ;

Troncoso-Escudero, Paulina ;

Wyneken, Ursula .

FRONTIERS IN CELLULAR NEUROSCIENCE, 2016, 9

[7] Middle meningeal artery embolization for the management of chronic subdural hematoma [J].

Fiorella, David ;

Arthur, Adam S. .

JOURNAL OF NEUROINTERVENTIONAL SURGERY, 2019, 11 (09) :912-915

[8] A Three-Day Consecutive Fingolimod Administration Improves Neurological Functions and Modulates Multiple Immune Responses of CCI Mice [J].

Gao, Chuang ;

Qian, Yu ;

Huang, Jinhao ;

Wang, Dong ;

Su, Wanqiang ;

Wang, Peng ;

Guo, Linyue ;

Quan, Wei ;

An, Shuo ;

Zhang, Jianning ;

Jiang, Rongcai .

MOLECULAR NEUROBIOLOGY, 2017, 54 (10) :8348-8360

[9] Possible tumor suppressive role of the miR-144/451 cluster in esophageal carcinoma as determined by principal component regression analysis [J].

Gao, Zhikui ;

Liu, Ran ;

Liao, Juan ;

Yang, Miao ;

Pan, Enchun ;

Yin, Lihong ;

Pu, Yuepu .

MOLECULAR MEDICINE REPORTS, 2016, 14 (04) :3805-3813

[10] Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis [J].

Gong, Min ;

Yu, Bin ;

Wang, Jingcai ;

Wang, Yigang ;

Liu, Min ;

Paul, Christian ;

Millard, Ronald W. ;

Xiao, De-Sheng ;

Ashraf, Muhammad ;

Xu, Meifeng .

ONCOTARGET, 2017, 8 (28) :45200-45212

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