Emilin1 Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature
Mol Cell Biol. 2008 Apr 14
Danussi C, Spessotto P, Petrucco A, Wassermann B, Sabatelli P, Montesi M, Doliana R, Bressan GM, Colombatti A.
Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS, Aviano, Pordenone, Italy; IGM-CNR, Unit of Bologna c/o IOR, Bologna, Italy; Mouse Genetics Laboratory, Department of Histology Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy; Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy; and MATI Center of Excellence, University of Udine, Udine, Italy.
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 been poorly taken into consideration when studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril associated protein, is highly expressed by LECs in vitro and co-localizes with lymphatic vessels in several mouse tissues. A comparative study between wild-type and Emilin1(-/-) mice highlighted that Emilin1 deficiency in both CD1 and C57BL/6 background results in hyperplasia, enlargement and frequently irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. Emilin1-deficient mice also develop larger lymphangiomas than wild-type mice. Lymphatic vascular morphological alterations are accompanied by functional defects such as mild lymphedema, 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 an 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.