title: Emilin1 deficiency causes structural and functional defects of lymphatic vasculature.
abstract: Lymphatic-vasculature function critically depends on extracellular matrix (ECM) and on its connections with lymphatic endothelial cells (LECs). However, the composition and the architecture of ECM have not been fully taken into consideration in studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril-associated protein, is highly expressed by LECs in vitro and colocalizes with lymphatic vessels in several mouse tissues. A comparative study between WT and Emilin1-/- mice highlighted the fact that Emilin1 deficiency in both CD1 and C57BL/6 backgrounds results in hyperplasia, enlargement, and frequently an irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. Emilin1-deficient mice also develop larger lymphangiomas than WT mice. Lymphatic vascular morphological alterations are accompanied by functional defects, such as mild lymphedema, a highly significant drop in lymph drainage, and enhanced lymph leakage. Our findings demonstrate that EMILIN1 is involved in the regulation of the growth and in the maintenance of the integrity of lymphatic vessels, a fundamental requirement for efficient function. The phenotype displayed by Emilin1(-/-) mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis.
authors.affiliation: Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS, Aviano, Pordenone, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Danussi
authors.forename: Paola
authors.initials: P
authors.lastname: Spessotto
authors.forename: Alessandra
authors.initials: A
authors.lastname: Petrucco
authors.forename: Bruna
authors.initials: B
authors.lastname: Wassermann
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sabatelli
authors.forename: Monica
authors.initials: M
authors.lastname: Montesi
authors.forename: Roberto
authors.initials: R
authors.lastname: Doliana
authors.forename: Giorgio M
authors.initials: GM
authors.lastname: Bressan
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010641:Phenotype
chemical_list: D008562:Membrane Glycoproteins; C030340:elastin microfibril interface located protein