EMILIN1/α9β1 integrin interaction is crucial in lymphatic valve formation and maintenance

Carla Danussi, Lisa Del Bel Belluz, Eliana Pivetta, Teresa Maria Elisa Modica, Andres Muro, Bruna Wassermann, Roberto Doliana, Patrizia Sabatelli, Alfonso Colombatti, Paola Spessotto

Research output: Contribution to journalArticle

Abstract

Lymphatic vasculature plays a crucial role in the maintenance of tissue interstitial fluid balance. The role of functional collecting lymphatic vessels in lymph transport has been recently highlighted in pathologies leading to lymphedema, for which treatments are currently unavailable. Intraluminal valves are of paramount importance in this process. However, valve formation and maturation have not been entirely elucidated yet, in particular, the role played by the extracellular matrix (ECM). We hypothesized that EMILIN1, an ECM multidomain glycoprotein, regulates lymphatic valve formation and maintenance. Using a mouse knockout model, we show that in the absence of EMILIN1, mice exhibit defects in lymphatic valve structure and in lymph flow. By applying morphometric in vitro and in vivo functional assays, we conclude that this impaired phenotype depends on the lack of α9β1 integrin engagement, the specific lymphatic endothelial cell receptor for EMILIN1, and the ensuing derangement of cell proliferation and migration. Our data demonstrate a fundamental role for EMILIN1-integrin α9 interaction in lymphatic vasculature, especially in lymphatic valve formation and maintenance, and underline the importance of this ECM component in displaying a regulatory function in proliferation and acting as a "guiding" molecule in migration of lymphatic endothelial cells.

Original languageEnglish
Pages (from-to)4381-4394
Number of pages14
JournalMolecular and Cellular Biology
Volume33
Issue number22
DOIs
Publication statusPublished - Nov 15 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Danussi, C., Belluz, L. D. B., Pivetta, E., Modica, T. M. E., Muro, A., Wassermann, B., Doliana, R., Sabatelli, P., Colombatti, A., & Spessotto, P. (2013). EMILIN1/α9β1 integrin interaction is crucial in lymphatic valve formation and maintenance. Molecular and Cellular Biology, 33(22), 4381-4394. https://doi.org/10.1128/MCB.00872-13.