title: Vascular endothelial growth factor-d modulates caliber and function of initial lymphatics in the dermis.
abstract: The lymphatic vasculature is important for skin biology as it maintains dermal fluid homeostasis. However, the molecular determinants of the form and function of the lymphatic vasculature in skin are poorly understood. Here, we explore the role of vascular endothelial growth factor-d (Vegf-d), a lymphangiogenic glycoprotein, in determining the form and function of the dermal lymphatic network, using Vegf-d-deficient mice. Initial lymphatic vessels in adult Vegf-d-deficient mice were significantly smaller than wild-type but collecting lymphatics were unaltered. The uptake/transport of dextran in initial lymphatics of Vegf-d-deficient mice was far less efficient, indicating compromised function of these vessels. The role of Vegf-d in modulating initial lymphatics was further supported by delivery of Vegf-d in skin of wild-type mice, which promoted enlargement of these vessels. Vegf-d-deficient mice were subjected to cutaneous wounding to challenge lymphatic function: the resulting wound epithelium was highly edematous and thicker, reflecting inadequate lymphatic drainage. Unexpectedly, myofibroblasts were more abundant in Vegf-d-deficient wounds leading to faster wound closure, but resorption of granulation tissue was compromised suggesting poorer-quality healing. Our findings demonstrate that Vegf-d deficiency alters the caliber of initial lymphatics in the dermis leading to reduced functional capacity.
authors: Tumour Angiogenesis Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors: Sophie
authors: S
authors: Paquet-Fifield
authors: Sidney M
authors: SM
authors: Levy
authors: Teruhiko
authors: T
authors: Sato
authors: Ramin
authors: R
authors: Shayan
authors: Tara
authors: T
authors: Karnezis
authors: Natalia
authors: N
authors: Davydova
authors: Cameron J
authors: CJ
authors: Nowell
authors: Sally
authors: S
authors: Roufail
authors: Gerry Zhi-Ming
authors: GZ
authors: Ma
authors: You-Fang
authors: YF
authors: Zhang
authors: Steven A
authors: SA
authors: Stacker
authors: Marc G
authors: MG
authors: Achen
mesh_terms: D000367:Age Factors; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D020405:Dermis / Q000098:blood supply / Q000293:injuries / Q000502:physiology*; D005260:Female; D006097:Granulation Tissue / Q000502:physiology; D042601:Lymphatic Vessels / Q000002:abnormalities* / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D042643:Vascular Endothelial Growth Factor D / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D042643:Vascular Endothelial Growth Factor D