Emilin1 deficiency causes structural and functional defects of lymphatic vasculature

Carla Danussi, Paola Spessotto, Alessandra Petrucco, Bruna Wassermann, Patrizia Sabatelli, Monica Montesi, Roberto Doliana, Giorgio M. Bressan, Alfonso Colombatti

Research output: Contribution to journalArticle

76 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4026-4039
Number of pages14
JournalMolecular and Cellular Biology
Volume28
Issue number12
DOIs
Publication statusPublished - Jun 2008

Fingerprint

Lymphatic Vessels
Lymph
Extracellular Matrix
Endothelial Cells
Lymphangiogenesis
Microfibrils
Phenotype
Lymphangioma
Lymphatic System
Lymphedema
Extracellular Matrix Proteins
Hyperplasia
Blood Vessels
Drainage
Maintenance
Pathology
Growth
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Emilin1 deficiency causes structural and functional defects of lymphatic vasculature. / Danussi, Carla; Spessotto, Paola; Petrucco, Alessandra; Wassermann, Bruna; Sabatelli, Patrizia; Montesi, Monica; Doliana, Roberto; Bressan, Giorgio M.; Colombatti, Alfonso.

In: Molecular and Cellular Biology, Vol. 28, No. 12, 06.2008, p. 4026-4039.

Research output: Contribution to journalArticle

Danussi, Carla ; Spessotto, Paola ; Petrucco, Alessandra ; Wassermann, Bruna ; Sabatelli, Patrizia ; Montesi, Monica ; Doliana, Roberto ; Bressan, Giorgio M. ; Colombatti, Alfonso. / Emilin1 deficiency causes structural and functional defects of lymphatic vasculature. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 12. pp. 4026-4039.
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