VEGF‐A promotes tissue repair‐associated lymphatic vessel formation via VEGFR‐2 and the α1β1 and α2β1 integrins

Wiley - Tập 18 Số 10 - Trang 1111-1113 - 2004
Young‐Kwon Hong1, Bernhard Lange‐Asschenfeldt1, Paula Velasco1, Satoshi Hirakawa1, Rainer Kunstfeld1, Lawrence F. Brown2, Peter Böhlen3, Donald R. Senger2, Michael Detmar1
1Cutaneous Biology Research CenterDepartment of DermatologyMassachusetts General Hospital and Harvard Medical SchoolCharlestownMassachusetts
2Department of PathologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMassachusetts
3ImClone Systems IncorporatedNew YorkNew York

Tóm tắt

ABSTRACTVascular endothelial growth factor‐A (VEGF‐A) is strongly up‐regulated in wounded cutaneous tissue and promotes repair‐associated angiogenesis. However, little is known about its role in lymphatic regeneration of the healing skin. We studied wound healing in transgenic mice that overexpress VEGF‐A specifically in the epidermis and in wild‐type mice in the absence or presence of inhibitors of VEGF‐A signaling. Surprisingly, transgenic overexpression of VEGF‐A in the skin promoted lymphangiogenesis at the wound healing site, whereas systemic blockade of VEGFR‐2 prevented lymphatic vessel formation. Studies in cultured lymphatic endothelial cells revealed that VEGF‐A induced expression of the α1 and α2 integrins, which promoted their in vitro tube formation and their haptotactic migration toward type I collagen. VEGF‐A‐induced lymphatic endothelial cord formation and haptotactic migration were suppressed by anti‐α1 and anti‐α2 integrin blocking antibodies, and systemic blockade of the α1 and α2 integrins inhibited VEGF‐A‐driven lymphangiogenesis in vivo. We propose that VEGF‐A promotes lymphatic vasculature formation via activation of VEGFR‐2 and that lineage‐specific differences of integrin receptor expression contribute to the distinct dynamics of wound‐associated angiogenesis and lymphangiogenesis.

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Wiley

Tập 18 Số 10

1111-1113

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