Perivascular cells regulate endothelial membrane type-1 matrix metalloproteinase activity

Lafleur, M.A., Forsyth, P.A., Atkinson, S.J., Murphy, G. and Edwards, D.R. ORCID: https://orcid.org/0000-0002-3292-2064 (2001) Perivascular cells regulate endothelial membrane type-1 matrix metalloproteinase activity. Biochemical and Biophysical Research Communications, 282 (2). pp. 463-473. ISSN 1090-2104

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Abstract

Angiogenic stimuli selectively induced expression of membrane type-1 matrix metalloproteinase (MT1-MMP) transcripts and protein in human umbilical vein endothelial cells (HUVECs). Pro-MMP-2 activation was blocked by treatment with tissue inhibitor of metalloproteinases-2 (TIMP-2), but not by TIMP-1 or inhibitors of other proteinase classes. Anti-MT1-MMP antibodies abrogated recombinant pro-MMP-2 activation by plasma membranes, indicating that MT1-MMP is the main mediator of pro-MMP-2 activation in HUVECs. Cocultures of HUVECs with smooth muscle cells (SMC) or pericytes (PC) resulted in the suppression of HUVEC pro-MMP-2 activation. Treatment of A10 SMC conditioned media with a neutralising anti-TIMP-2 antibody prevented the suppression of HUVEC pro-MMP-2 activation. Inhibition of HUVEC MT1-MMP function by PC and SM3 SMC correlated with elevated TIMP-3 expression. Thus, perivascular supporting cells regulate the functions of proangiogenic MMPs elaborated by endothelial cells via selective expression of TIMPs. This interplay may be important for maintenance of blood vessel architecture and neovascularisation.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Depositing User:	EPrints Services
Date Deposited:	01 Oct 2010 13:36
Last Modified:	24 Sep 2024 10:23
URI:	https://ueaeprints.uea.ac.uk/id/eprint/61
DOI:	10.1006/bbrc.2001.4596

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