Akt/protein kinase B is required for lymphatic network formation, remodeling, and valve development
Date
2010
Authors
Zhou, F.
Chang, Z.
Zhang, L.
Hong, Y.K.
Shen, B.
Wang, B.
Zhang, F.
Lu, G.
Tvorogov, D.
Alitalo, K.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
American Journal of Pathology, 2010; 177(4):2124-2133
Statement of Responsibility
Conference Name
Abstract
Akt-mediated signaling plays an important role in blood vascular development. In this study, we investigated the role of Akt in lymphatic growth using Akt-deficient mice. First, we found that lymphangiogenesis occurred in Akt1-/-, Akt2-/-, and Akt3-/- mice. However, both the diameter and endothelial cell number of lymphatic capillaries were significantly less in Akt1-/- mice than in wild-type control mice, whereas there was only a slight change in Akt2-/- and Akt3 -/- mice. Second, valves present in the small collecting lymphatics in the superficial dermal layer of the ear skin were rarely observed in Akt1-/- mice, although these valves could be detected in the large collecting lymphatics in the deep layer of the skin tissues. A fluorescence microlymphangiography assay showed that the skin lymphatic network in Akt1 -/- mice was functional but abnormal as shown by fluorescein isothiocyanate-dextran draining.
There was an uncharacteristic enlargement of collecting lymphatic vessels, and further analysis showed that smooth muscle cell coverage of collecting lymphatic vessels became much more sparse in Akt1-deficient mice than in wild-type control animals. Finally, we showed that lymphatic vessels were detected in compound Akt-null mice and that lymphangiogenesis could be induced by vascular endothelial growth factor-C delivered via adenoviral vectors in adult mice lacking Akt1. These results indicate that despite the compensatory roles of other Akt isoforms, Akt1 is more critically required during lymphatic development.
School/Discipline
Dissertation Note
Provenance
Description
Link to a related website: http://europepmc.org/articles/pmc2947305?pdf=render, Open Access via Unpaywall
Access Status
Rights
Copyright 2010 American Society for Investigative Pathology