Akt/Protein Kinase B Is Required for Lymphatic Network Formation, Remodeling, and Valve Development.
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Zhou, Fei, Chang, Zai, Zhang, Luqing, Hong, Young-Kwon, Shen, Bin, Wang, Bo, Zhang, Fan, Lu, Guangming, Tvorogov, Denis, Alitalo, Kari, Hemmings, Brian Arthur, Yang, Zhongzhou and He, Yulong (2010) Akt/Protein Kinase B Is Required for Lymphatic Network Formation, Remodeling, and Valve Development. The American Journal of Pathology. ISSN 0002-9440
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.
| Item Type: | Article |
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| Date Deposited: | 11 Oct 2010 23:45 |
| Last Modified: | 01 Feb 2013 00:48 |
| URI: | https://oak.novartis.com/id/eprint/3757 |