Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption

Samira Saadoun, Marios C. Papadopoulos, Mariko Hara-Chikuma, A. S. Verkman

研究成果: Article

572 引用 (Scopus)

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Aquaporin-1 (AQP1) is a water channel protein expressed widely in vascular endothelia, where it increases cell membrane water permeability. The role of AQP1 in endothelial cell function is unknown.Here we show remarkably impaired tumour growth in AQP1-null mice after subcutaneous or intracranial tumour cell implantation, with reduced tumour vascularity and extensive necrosis. A new mechanism for the impaired angiogenesis was established from cell culture studies. Although adhesion and proliferation were similar in primary cultures of aortic endothelia from wild-type and from AQP1-null mice, cell migration was greatly impaired in AQP1-deficient cells, with abnormal vessel formation in vitro. Stable transfection of non-endothelial cells with AQP1 or with a structurally different water-selective trans porter (AQP4) accelerated cell migration and wound healing in vitro.Motile AQP1-expressing cells had prominent membrane ruffles at the leading edge with polarization of AQP1 protein to lamellipodia, where rapid water fluxes occur. Our findings support a fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration.

元の言語English
ページ(範囲)786-792
ページ数7
ジャーナルNature
434
発行部数7034
DOI
出版物ステータスPublished - 2005 4 7
外部発表Yes

ASJC Scopus subject areas

  • General

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