Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells

被引:201
作者
Atienzar-Aroca, Sandra [1 ]
Flores-Bellver, Miguel [1 ,2 ]
Serrano-Heras, Gemma [3 ]
Martinez-Gil, Natalia [1 ]
Barcia, Jorge M. [1 ]
Aparicio, Silvia [4 ]
Perez-Cremades, Daniel [5 ]
Garcia-Verdugo, Jose M. [6 ]
Diaz-Llopis, Manuel [7 ]
Romero, Francisco J. [1 ]
Sancho-Pelluz, Javier [1 ]
机构
[1] Catholic Univ Valencia, Sch Med, Valencia, Spain
[2] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA
[3] Gen Univ Hosp Albacete, Expt Res Unit, Albacete, Spain
[4] CSIC, Valencian Biomed Inst, Valencia, Spain
[5] Univ Valencia, Dept Physiol, Valencia, Spain
[6] Univ Valencia, Dept Comparat Neurobiol, Cavanilles Inst Biodivers & Evolut Biol, Valencia, Spain
[7] Univ Valencia, Dept Surg, Valencia, Spain
关键词
exosomes; retinal pigment epithelium; oxidative stress; angiogenesis; VEGF receptors; GROWTH-FACTOR; VEGF; BIOGENESIS; AUTOPHAGY; RECEPTOR; NEOVASCULARIZATION; MECHANISMS; EXPRESSION; VESICLES; ALCOHOL;
D O I
10.1111/jcmm.12834
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The retinal pigment epithelium (RPE), a monolayer located between the photoreceptors and the choroid, is constantly damaged by oxidative stress, particularly because of reactive oxygen species (ROS). As the RPE, because of its physiological functions, is essential for the survival of the retina, any sustained damage may consequently lead to loss of vision. Exosomes are small membranous vesicles released into the extracellular medium by numerous cell types, including RPE cells. Their cargo includes genetic material and proteins, making these vesicles essential for cell-to-cell communication. Exosomes may fuse with neighbouring cells influencing their fate. It has been observed that RPE cells release higher amounts of exosomes when they are under oxidative stress. Exosomes derived from cultured RPE cells were isolated by ultracentrifugation and quantified by flow cytometry. VEGF receptors (VEGFR) were analysed by both flow cytometry and Western blot. RT-PCR and qPCR were conducted to assess mRNA content of VEGFRs in exosomes. Neovascularization assays were performed after applying RPE exosomes into endothelial cell cultures. Our results showed that stressed RPE cells released a higher amount of exosomes than controls, with a higher expression of VEGFR in the membrane, and enclosed an extra cargo of VEGFR mRNA. Angiogenesis assays confirmed that endothelial cells increased their tube formation capacity when exposed to stressed RPE exosomes.
引用
收藏
页码:1457 / 1466
页数:10
相关论文
共 56 条
[1]   Exosomes with immune modulatory features are present in human breast milk [J].
Admyre, Charlotte ;
Johansson, Sara M. ;
Qazi, Khaleda Rahman ;
Filen, Jan-Jonas ;
Lahesmaa, Riitta ;
Norman, Mikael ;
Neve, Etienne P. A. ;
Scheynius, Annika ;
Gabrielsson, Susanne .
JOURNAL OF IMMUNOLOGY, 2007, 179 (03) :1969-1978
[2]   HYPOXIC REGULATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN RETINAL CELLS [J].
AIELLO, LP ;
NORTHRUP, JM ;
KEYT, BA ;
TAKAGI, H ;
IWAMOTO, MA .
ARCHIVES OF OPHTHALMOLOGY, 1995, 113 (12) :1538-1544
[3]   In vitro evaluation of endothelial exosomes as carriers for small interfering ribonucleic acid delivery [J].
Banizs, Anna B. ;
Huang, Tao ;
Dryden, Kelly ;
Berr, Stuart S. ;
Stone, James R. ;
Nakamoto, Robert K. ;
Shi, Weibin ;
He, Jiang .
INTERNATIONAL JOURNAL OF NANOMEDICINE, 2014, 9 :4223-4230
[4]   VEGF-Directed Blood Vessel Patterning: From Cells to Organism [J].
Bautch, Victoria L. .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2012, 2 (09)
[5]   Retinal pigment epithelium (RPE) exosomes contain signaling phosphoproteins affected by oxidative stress [J].
Biasutto, Lucia ;
Chiechi, Antonella ;
Couch, Robin ;
Liotta, Lance A. ;
Espina, Virginia .
EXPERIMENTAL CELL RESEARCH, 2013, 319 (13) :2113-2123
[6]   On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response [J].
Bonet-Ponce, Luis ;
Saez-Atienzar, Sara ;
da Casa, Carmen ;
Flores-Bellver, Miguel ;
Barcia, Jorge M. ;
Sancho-Pelluz, Javier ;
Romero, Francisco J. ;
Jordan, Joaquin ;
Galindo, Maria F. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2015, 1852 (07) :1400-1409
[7]   Alcohol linked to enhanced angiogenesis in rat model of choroidal neovascularization [J].
Bora, PS ;
Kaliappan, S ;
Xu, Q ;
Kumar, S ;
Wang, YL ;
Kaplan, HJ ;
Bora, NS .
FEBS JOURNAL, 2006, 273 (07) :1403-1414
[8]  
Boyer MM, 2000, ARCH OPHTHALMOL-CHIC, V118, P27
[9]   An affordable method to obtain cultured endothelial cells from peripheral blood [J].
Bueno-Beti, Carlos ;
Novella, Susana ;
Lazaro-Franco, Macarena ;
Perez-Cremades, Daniel ;
Heras, Magda ;
Sanchis, Juan ;
Hermenegildo, Carlos .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2013, 17 (11) :1475-1483
[10]   Exosomal-like vesicles are present in human blood plasma [J].
Caby, MP ;
Lankar, D ;
Vincendeau-Scherrer, C ;
Raposo, G ;
Bonnerot, C .
INTERNATIONAL IMMUNOLOGY, 2005, 17 (07) :879-887