title: Akt/Protein kinase B is required for lymphatic network formation, remodeling, and valve development.
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.
authors: Laboratory of Vascular and Cancer Biology, MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, Nanjing, China.
authors: Fei
authors: F
authors: Zhou
authors: Zai
authors: Z
authors: Chang
authors: Luqing
authors: L
authors: Zhang
authors: Young-Kwon
authors: YK
authors: Hong
authors: Bin
authors: B
authors: Shen
authors: Bo
authors: B
authors: Wang
authors: Fan
authors: F
authors: Zhang
authors: Guangming
authors: G
authors: Lu
authors: Denis
authors: D
authors: Tvorogov
authors: Kari
authors: K
authors: Alitalo
authors: Brian A
authors: BA
authors: Hemmings
authors: Zhongzhou
authors: Z
authors: Yang
authors: Yulong
authors: Y
authors: He
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism; D052816:Foreskin / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
chemical_list: D042582:Vascular Endothelial Growth Factor C; C514862:Akt1 protein, mouse; C494922:Akt2 protein, mouse; C491753:Akt3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt