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Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice
Angiogenesis is a fundamental process during development and disease, and many details of the underlying molecular and cellular mechanisms are incompletely understood. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, has recently been i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073967/ https://www.ncbi.nlm.nih.gov/pubmed/27790365 http://dx.doi.org/10.1186/s13221-016-0038-2 |
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author | Napp, L. Christian Jabs, Olga Höckelmann, Anna Dutzmann, Jochen Kapopara, Piyush R. Sedding, Daniel G. Gaestel, Matthias Bauersachs, Johann Bavendiek, Udo |
author_facet | Napp, L. Christian Jabs, Olga Höckelmann, Anna Dutzmann, Jochen Kapopara, Piyush R. Sedding, Daniel G. Gaestel, Matthias Bauersachs, Johann Bavendiek, Udo |
author_sort | Napp, L. Christian |
collection | PubMed |
description | Angiogenesis is a fundamental process during development and disease, and many details of the underlying molecular and cellular mechanisms are incompletely understood. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, has recently been identified as a regulator of Interleukin 1β dependent angiogenesis in vivo, and in vitro data suggest a role of MK2 for VEGF-dependent angiogenic processes in endothelial cells. We thus hypothesized that MK2 plays a role during physiological vascular development in vivo. Vascular development was investigated in the retina of MK2-deficient mice. Retinal angiogenesis such as sprouting, branching and pruning was unchanged in MK2(-/-) mice compared to wildtype littermates. Early arterial development was also comparable between genotypes. However, with further expansion of vascular smooth muscle cells (SMC) during maturation of the arterial network at later time points, the number of arterial branch points was significantly lower in MK2(-/-) mice, resulting in a reduced total arterial area in adult mice. Isolated aortic smooth muscle cells from MK2(-/-) mice showed a more dedifferentiated phenotype in vitro and downregulation of central SMC marker genes, consistent with the known impaired migration of MK2(-/-) SMC. In conclusion, MK2 is not required for physiological retinal angiogenesis. However, its loss is associated with an altered genetic profile of SMC and an impaired arterial network in adult mice, indicating a distinct and probably cell-specific role of MK2 in arteries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13221-016-0038-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5073967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50739672016-10-27 Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice Napp, L. Christian Jabs, Olga Höckelmann, Anna Dutzmann, Jochen Kapopara, Piyush R. Sedding, Daniel G. Gaestel, Matthias Bauersachs, Johann Bavendiek, Udo Vasc Cell Letter to the Editor Angiogenesis is a fundamental process during development and disease, and many details of the underlying molecular and cellular mechanisms are incompletely understood. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, has recently been identified as a regulator of Interleukin 1β dependent angiogenesis in vivo, and in vitro data suggest a role of MK2 for VEGF-dependent angiogenic processes in endothelial cells. We thus hypothesized that MK2 plays a role during physiological vascular development in vivo. Vascular development was investigated in the retina of MK2-deficient mice. Retinal angiogenesis such as sprouting, branching and pruning was unchanged in MK2(-/-) mice compared to wildtype littermates. Early arterial development was also comparable between genotypes. However, with further expansion of vascular smooth muscle cells (SMC) during maturation of the arterial network at later time points, the number of arterial branch points was significantly lower in MK2(-/-) mice, resulting in a reduced total arterial area in adult mice. Isolated aortic smooth muscle cells from MK2(-/-) mice showed a more dedifferentiated phenotype in vitro and downregulation of central SMC marker genes, consistent with the known impaired migration of MK2(-/-) SMC. In conclusion, MK2 is not required for physiological retinal angiogenesis. However, its loss is associated with an altered genetic profile of SMC and an impaired arterial network in adult mice, indicating a distinct and probably cell-specific role of MK2 in arteries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13221-016-0038-2) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-21 /pmc/articles/PMC5073967/ /pubmed/27790365 http://dx.doi.org/10.1186/s13221-016-0038-2 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Letter to the Editor Napp, L. Christian Jabs, Olga Höckelmann, Anna Dutzmann, Jochen Kapopara, Piyush R. Sedding, Daniel G. Gaestel, Matthias Bauersachs, Johann Bavendiek, Udo Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice |
title | Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice |
title_full | Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice |
title_fullStr | Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice |
title_full_unstemmed | Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice |
title_short | Normal endothelial but impaired arterial development in MAP-Kinase activated protein kinase 2 (MK2) deficient mice |
title_sort | normal endothelial but impaired arterial development in map-kinase activated protein kinase 2 (mk2) deficient mice |
topic | Letter to the Editor |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073967/ https://www.ncbi.nlm.nih.gov/pubmed/27790365 http://dx.doi.org/10.1186/s13221-016-0038-2 |
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