| First Author | Zhou F | Year | 2010 |
| Journal | Am J Pathol | Volume | 177 |
| Issue | 4 | Pages | 2124-33 |
| PubMed ID | 20724596 | Mgi Jnum | J:165339 |
| Mgi Id | MGI:4837029 | Doi | 10.2353/ajpath.2010.091301 |
| Citation | Zhou F, et al. (2010) Akt/Protein kinase B is required for lymphatic network formation, remodeling, and valve development. Am J Pathol 177(4):2124-33 |
| abstractText | 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. |
