UZH-Logo

Maintenance Infos

Endothelial Rictor is crucial for midgestational development and sustained and extensive FGF2-induced neovascularization in the adult


Aimi, Fabio; Georgiopoulou, Stavroula; Kalus, Ina; Lehner, Fabienne; Hegglin, Alica; Limani, Përparim; Gomes de Lima, Vinicius; A Rüegg, Markus; Hall, Michael N; Lindenblatt, Nicole; Haas, Elvira; Battegay, Edouard J; Humar, Rok (2015). Endothelial Rictor is crucial for midgestational development and sustained and extensive FGF2-induced neovascularization in the adult. Scientific Reports, 5:17705.

Abstract

To explore the general requirement of endothelial mTORC2 during embryonic and adolescent development, we knocked out the essential mTORC2 component Rictor in the mouse endothelium in the embryo, during adolescence and in endothelial cells in vitro. During embryonic development, Rictor knockout resulted in growth retardation and lethality around embryonic day 12. We detected reduced peripheral vascularization and delayed ossification of developing fingers, toes and vertebrae during this confined midgestational period. Rictor knockout did not affect viability, weight gain, and vascular development during further adolescence. However during this period, Rictor knockout prevented skin capillaries to gain larger and heterogeneously sized diameters and remodeling into tortuous vessels in response to FGF2. Rictor knockout strongly reduced extensive FGF2-induced neovascularization and prevented hemorrhage in FGF2-loaded matrigel plugs. Rictor knockout also disabled the formation of capillary-like networks by FGF2-stimulated mouse aortic endothelial cells in vitro. Low RICTOR expression was detected in quiescent, confluent mouse aortic endothelial cells, whereas high doses of FGF2 induced high RICTOR expression that was associated with strong mTORC2-specific protein kinase Cα and AKT phosphorylation. We demonstrate that the endothelial FGF-RICTOR axis is not required during endothelial quiescence, but crucial for midgestational development and sustained and extensive neovascularization in the adult.

Abstract

To explore the general requirement of endothelial mTORC2 during embryonic and adolescent development, we knocked out the essential mTORC2 component Rictor in the mouse endothelium in the embryo, during adolescence and in endothelial cells in vitro. During embryonic development, Rictor knockout resulted in growth retardation and lethality around embryonic day 12. We detected reduced peripheral vascularization and delayed ossification of developing fingers, toes and vertebrae during this confined midgestational period. Rictor knockout did not affect viability, weight gain, and vascular development during further adolescence. However during this period, Rictor knockout prevented skin capillaries to gain larger and heterogeneously sized diameters and remodeling into tortuous vessels in response to FGF2. Rictor knockout strongly reduced extensive FGF2-induced neovascularization and prevented hemorrhage in FGF2-loaded matrigel plugs. Rictor knockout also disabled the formation of capillary-like networks by FGF2-stimulated mouse aortic endothelial cells in vitro. Low RICTOR expression was detected in quiescent, confluent mouse aortic endothelial cells, whereas high doses of FGF2 induced high RICTOR expression that was associated with strong mTORC2-specific protein kinase Cα and AKT phosphorylation. We demonstrate that the endothelial FGF-RICTOR axis is not required during endothelial quiescence, but crucial for midgestational development and sustained and extensive neovascularization in the adult.

Citations

3 citations in Web of Science®
3 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

8 downloads since deposited on 17 Dec 2015
8 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
04 Faculty of Medicine > University Hospital Zurich > Clinic for Reconstructive Surgery
08 University Research Priority Programs > Integrative Human Physiology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:17 Dec 2015 10:07
Last Modified:05 Apr 2016 19:39
Publisher:Nature Publishing Group
ISSN:2045-2322
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/srep17705
PubMed ID:26635098

Download

[img]
Preview
Content: Published Version
Filetype: PDF
Size: 2MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations