Exosomes from Retinal Astrocytes Contain Antiangiogenic Components That Inhibit Laser-induced Choroidal Neovascularization

Hajrasouliha, Amir Reza; Jiang, Guomin; Lu, Qin; Han, Lu; Kaplan, Henry J.; Zhang, Huang‐Ge; Shao, Hui

doi:10.1074/jbc.m113.470765

Cited by 123 publications

(119 citation statements)

References 43 publications

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“…Exosomes derived from astrocytes exhibit endostatin-dependent antiangiogenic properties that inhibit laser-induced choroidal neovascularization. 64 Increased oxidative stress and negative regulation of vascular endothelial growth factor pathways contribute to the antiangiogenic effect of lymphocytic microparticles. 65 Interestingly, identification of newly discovered microRNA cargos in circulating microvesicles and exosomes provides promising biomarkers of angiogenic potential in patients with critical limb ischemia or diabetes mellitus.…”

Section: Extracellular Microvesicles As Intercellular Messengersmentioning

confidence: 99%

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Loyer

Vion

Tedgui

et al. 2014

Circulation Research

364

299

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Section: Extracellular Microvesicles As Intercellular Messengersmentioning

confidence: 99%

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Loyer

Vion

Tedgui

et al. 2014

Circulation Research

364

299

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“…Nevertheless, it has been established that retinal astrocytes are able to counteract pro-angiogenic stimuli through releasing of exosomes loaded with angio-suppressors, i.e. endostatin and pigment-endothelium derived factor (PEDF) [19]. Meanwhile, astrocytes appeared to be capable of producing and secreting proteolytically active matrix metalloproteinases (MMP) and Pm, representing proteinases responsible for Pg cleavage and angiostatin formation [20].…”

Section: The Purpose Of the Present Study Was To Examine The Plasminomentioning

confidence: 99%

“…In respect of this, astrocytes are of particular interest due to the three reasons: 1) astrocytes are the most frequent cells in the CNS, which emulate the metabolic activity of neurons; 2) astrocytes play a pivo tal role as "communicators" between neurons and endotheliocytes; 3) astrocytes have been shown to produce and release several negative regulators of angiogenesis, i.e. endostatins, and have all the necessary proteinase and enzyme cascades to decompose Pg to yield angiostatins [17,19,20]. So far, there are no data available on this function of brain astrocytes.…”

Section: Fig 2 Representative Fluorescence Micrographs Of Plasminogmentioning

confidence: 99%

Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Tykhomyrov¹,

Nedzvetsky²,

Ağca³

et al. 2017

Ukr.Biochem.J.

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“…1E). These data indicate that intact exosomes were successfully isolated.Integrin β1 protein levels are downregulated by macrophage-derived exosomes in primary endothelial cells Recent reports have suggested that exosomes are potent regulators of cell migration through intercellular communication [26,27]. We determined the effect of macrophage-derived exosomes on endothelial cells by isolating macrophage exosomes from the conditioned medium of differentiated THP1 cells.…”

mentioning

confidence: 99%

Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking

Lee

Kim

2014

Eur J Immunol

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Integrin trafficking, including internalization, recycling, and lysosomal degradation, is crucial for the regulation of cellular functions. Exosomes, nano-sized extracellular vesicles, are believed to play important roles in intercellular communications. This study demonstrates that exosomes released from human macrophages negatively regulate endothelial cell migration through control of integrin trafficking. Macrophage-derived exosomes promote internalization of integrin β1 in primary HUVECs. The internalized integrin β1 persistently accumulates in the perinuclear region and is not recycled back to the plasma membrane. Experimental results indicate that macrophage-derived exosomes stimulate trafficking of internalized integrin β1 to lysosomal compartments with a corresponding decrease in the integrin destined for recycling endosomes, resulting in proteolytic degradation of the integrin. Moreover, ubiquitination of HUVEC integrin β1 is enhanced by the exosomes, and exosome-mediated integrin degradation is blocked by bafilomycin A, a lysosomal degradation inhibitor. Macrophage-derived exosomes were also shown to effectively suppress collagen-induced activation of the mitogenactivated protein kinase/extracellular signal-regulated kinase signaling pathway and HUVEC migration, which are both dependent on integrin β1. These observations provide new insight into the functional significance of exosomes in the regulation of integrin trafficking. Keywords: Endothelial cell migration r Exosomes r Integrin trafficking r MacrophagesAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionIntegrin, a heterodimeric transmembrane receptor composed of α-and β-subunits, has a fundamental role in communication between cells and the extracellular matrix [1,2]. Recent studies have shown that trafficking of integrin is a crucial step in this communication [3][4][5]. Integrin is regularly internalized via the endocytosis pathway and internalized integrin is recycled back to the plasma membrane [3,4]. Internalized integrin β1, the most widely expressed integrin subunit, accumulates in the perinuclear Correspondence: Dr. Doo-Sik Kim e-mail: dskim@yonsei.ac.kr region of cells and is returned to the plasma membrane through RAB11-positive recycling endosomes [3]. The recycling process rearranges the distribution of integrins on the cell surface and controls the direction of cell migration [3]. Ubiquitination of integrin acts as a signal to trigger trafficking of internalized integrin to the lysosomal degradation compartment [5,6]. The degradation process is important for controlling the proper expression level of integrin on the cell surface, by which cell-matrix association and cell migration are tightly regulated [5,7].Integrin is a key regulator of cellular functions associated with vascular processes [8,9]. Endothelial cell migration and leukocyte recruitment during inflammation are tightly controlled by integrin functions. The expression and activation of integrins C...

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Exosomes from Retinal Astrocytes Contain Antiangiogenic Components That Inhibit Laser-induced Choroidal Neovascularization

Cited by 123 publications

References 43 publications

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking

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