Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Chi Hsiu Liu, Ye Sun, Jie Li, Yan Gong, Katherine T. Tian, Lucy P. Evans, Peyton C. Morss, Thomas W. Fredrick, Nicholas J. Saba, Jing Chen, Jeremy Nathans

Research output: Contribution to journalArticle

Abstract

Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.

Original languageEnglish (US)
Pages (from-to)12163-12168
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number39
DOIs
StatePublished - Sep 29 2015

Fingerprint

Pathologic Neovascularization
MicroRNAs
Endothelial Cells
Physiologic Neovascularization
Retinal Neovascularization
Retinal Vessels
Choroidal Neovascularization
Intravitreal Injections
Eye Diseases
Blindness
Vascular Diseases
Knockout Mice
Endothelium
Cell Movement
Blood Vessels
Lasers
Cell Proliferation
Oxygen
Gene Expression

Keywords

  • Endothelial cells
  • MicroRNA
  • MiR-150
  • Neovascularization
  • Retinopathy

ASJC Scopus subject areas

  • General

Cite this

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization. / Liu, Chi Hsiu; Sun, Ye; Li, Jie; Gong, Yan; Tian, Katherine T.; Evans, Lucy P.; Morss, Peyton C.; Fredrick, Thomas W.; Saba, Nicholas J.; Chen, Jing; Nathans, Jeremy.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 39, 29.09.2015, p. 12163-12168.

Research output: Contribution to journalArticle

Liu, Chi Hsiu ; Sun, Ye ; Li, Jie ; Gong, Yan ; Tian, Katherine T. ; Evans, Lucy P. ; Morss, Peyton C. ; Fredrick, Thomas W. ; Saba, Nicholas J. ; Chen, Jing ; Nathans, Jeremy. / Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 39. pp. 12163-12168.
@article{5682b3f097bd4c2386652e67055cbf1e,
title = "Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization",
abstract = "Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.",
keywords = "Endothelial cells, MicroRNA, MiR-150, Neovascularization, Retinopathy",
author = "Liu, {Chi Hsiu} and Ye Sun and Jie Li and Yan Gong and Tian, {Katherine T.} and Evans, {Lucy P.} and Morss, {Peyton C.} and Fredrick, {Thomas W.} and Saba, {Nicholas J.} and Jing Chen and Jeremy Nathans",
year = "2015",
month = "9",
day = "29",
doi = "10.1073/pnas.1508426112",
language = "English (US)",
volume = "112",
pages = "12163--12168",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "39",

}

TY - JOUR

T1 - Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

AU - Liu, Chi Hsiu

AU - Sun, Ye

AU - Li, Jie

AU - Gong, Yan

AU - Tian, Katherine T.

AU - Evans, Lucy P.

AU - Morss, Peyton C.

AU - Fredrick, Thomas W.

AU - Saba, Nicholas J.

AU - Chen, Jing

AU - Nathans, Jeremy

PY - 2015/9/29

Y1 - 2015/9/29

N2 - Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.

AB - Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.

KW - Endothelial cells

KW - MicroRNA

KW - MiR-150

KW - Neovascularization

KW - Retinopathy

UR - http://www.scopus.com/inward/record.url?scp=84942924088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942924088&partnerID=8YFLogxK

U2 - 10.1073/pnas.1508426112

DO - 10.1073/pnas.1508426112

M3 - Article

C2 - 26374840

AN - SCOPUS:84942924088

VL - 112

SP - 12163

EP - 12168

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 39

ER -