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miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo

Pedrioli, D. M. and Karpanen, T. and Dabouras, V. and Jurisic, G. and Hoek van de, G. and Shin, J. W. and Marino, D. and Kalin, R. E. and Leidel, S. and Cinelli, P. and Schulte-Merker, S. and Brandli, A. W. and Detmar, M. (2010) miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo. Molecular and Cellular Biology, 30, 3620-34. ISSN 0270-7306.

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Official URL: http://dx.doi.org/10.1128/mcb.00185-10

Abstract

The lymphatic vascular system maintains tissue fluid homeostasis, helps mediate afferent immune responses, and promotes cancer metastasis. To address the role microRNAs (miRNAs) play in the development and function of the lymphatic vascular system, we defined the in vitro miRNA expression profiles of primary human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs) and identified four BVEC signature and two LEC signature miRNAs. Their vascular lineage-specific expression patterns were confirmed in vivo by quantitative real-time PCR and in situ hybridization. Functional characterization of the BVEC signature miRNA miR-31 identified a novel BVEC-specific posttranscriptional regulatory mechanism that inhibits the expression of lymphatic lineage-specific transcripts in vitro. We demonstrate that suppression of lymphatic differentiation is partially mediated via direct repression of PROX1, a transcription factor that functions as a master regulator of lymphatic lineage-specific differentiation. Finally, in vivo studies of Xenopus and zebrafish demonstrated that gain of miR-31 function impaired venous sprouting and lymphatic vascular development, thus highlighting the importance of miR-31 as a negative regulator of lymphatic development. Collectively, our findings identify miR-31 is a potent regulator of vascular lineage-specific differentiation and development in vertebrates.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:9518
Deposited On:07 Feb 2011 01:00
Last Modified:07 Sep 2011 17:01

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