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Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila

The blood-brain barrier (BBB) is an essential system that isolates the central nervous system from the internal environment. Increasing evidence has begun to reveal the molecules that are required for BBB integrity. However, how these components are regulated remains unclear. Here we report that a m...

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Autores principales: Kanda, Hiroshi, Shimamura, Rieko, Koizumi-Kitajima, Michiko, Okano, Hideyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562144/
https://www.ncbi.nlm.nih.gov/pubmed/31195239
http://dx.doi.org/10.1016/j.isci.2019.05.027
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author Kanda, Hiroshi
Shimamura, Rieko
Koizumi-Kitajima, Michiko
Okano, Hideyuki
author_facet Kanda, Hiroshi
Shimamura, Rieko
Koizumi-Kitajima, Michiko
Okano, Hideyuki
author_sort Kanda, Hiroshi
collection PubMed
description The blood-brain barrier (BBB) is an essential system that isolates the central nervous system from the internal environment. Increasing evidence has begun to reveal the molecules that are required for BBB integrity. However, how these components are regulated remains unclear. Here we report that a matrix metalloproteinase, Mmp2, is essential for the establishment of the BBB in Drosophila. In the absence of mmp2, the BBB becomes leaky, which allows the tracer to penetrate the brain. Moreover, the expression pattern of a junctional component, Neuroglian, is altered. We also find that the regulation of the amounts of particular extracellular matrix components is critical for BBB establishment. Furthermore, the process of mesenchymal-epithelial transition of BBB-forming cells is perturbed in the absence of Mmp2. These data indicate that the presence of Mmp(s), which is typically considered to be a risk factor for BBB degradation, is essential for BBB integrity in Drosophila.
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spelling pubmed-65621442019-06-17 Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila Kanda, Hiroshi Shimamura, Rieko Koizumi-Kitajima, Michiko Okano, Hideyuki iScience Article The blood-brain barrier (BBB) is an essential system that isolates the central nervous system from the internal environment. Increasing evidence has begun to reveal the molecules that are required for BBB integrity. However, how these components are regulated remains unclear. Here we report that a matrix metalloproteinase, Mmp2, is essential for the establishment of the BBB in Drosophila. In the absence of mmp2, the BBB becomes leaky, which allows the tracer to penetrate the brain. Moreover, the expression pattern of a junctional component, Neuroglian, is altered. We also find that the regulation of the amounts of particular extracellular matrix components is critical for BBB establishment. Furthermore, the process of mesenchymal-epithelial transition of BBB-forming cells is perturbed in the absence of Mmp2. These data indicate that the presence of Mmp(s), which is typically considered to be a risk factor for BBB degradation, is essential for BBB integrity in Drosophila. Elsevier 2019-05-27 /pmc/articles/PMC6562144/ /pubmed/31195239 http://dx.doi.org/10.1016/j.isci.2019.05.027 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kanda, Hiroshi
Shimamura, Rieko
Koizumi-Kitajima, Michiko
Okano, Hideyuki
Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila
title Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila
title_full Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila
title_fullStr Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila
title_full_unstemmed Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila
title_short Degradation of Extracellular Matrix by Matrix Metalloproteinase 2 Is Essential for the Establishment of the Blood-Brain Barrier in Drosophila
title_sort degradation of extracellular matrix by matrix metalloproteinase 2 is essential for the establishment of the blood-brain barrier in drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562144/
https://www.ncbi.nlm.nih.gov/pubmed/31195239
http://dx.doi.org/10.1016/j.isci.2019.05.027
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