2024-03-29T14:57:37Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/96312023-10-09T08:07:59Zcom_20.500.12105_2152com_20.500.12105_2051com_20.500.12105_2144com_20.500.12105_2145col_20.500.12105_2153col_20.500.12105_2146
Repisalud
author
Esteban, Sergio
author
Clemente, Cristina
author
Koziol, Agnieszka
author
Gonzalo, Pilar
author
Rius, Cristina
author
Martinez, Fernando
author
Linares, Pablo M
author
Chaparro, María
author
Urzainqui, Ana
author
Andres, Vicente
author
Seiki, Motoharu
author
Gisbert, Javier P
author
Arroyo, Alicia G
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
2020-04-20T13:21:54Z
2020-04-20T13:21:54Z
2020-02
EMBO Mol Med. 2020; 12(2):e10862
1757-4676
http://hdl.handle.net/20.500.12105/9631
31793743
10.15252/emmm.201910862
1757-4684
EMBO molecular medicine
Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre-existing capillaries. In this report, mice lacking the protease MT1-MMP in endothelial cells (MT1iΔEC ) presented limited IA in the capillary plexus of the colon mucosa assessed by 3D imaging during 1% DSS-induced colitis. This resulted in better tissue perfusion, preserved intestinal morphology, and milder disease activity index. Combined in vivo intravital microscopy and lentiviral rescue experiments with in vitro cell culture demonstrated that MT1-MMP activity in endothelial cells is required for vasodilation and IA, as well as for nitric oxide production via binding of the C-terminal fragment of MT1-MMP substrate thrombospondin-1 (TSP1) to CD47/αvβ3 integrin. Moreover, TSP1 levels were significantly higher in serum from IBD patients and in vivo administration of an anti-MT1-MMP inhibitory antibody or a nonamer peptide spanning the αvβ3 integrin binding site in TSP1 reduced IA during mouse colitis. Our results identify MT1-MMP as a new actor in inflammatory IA and a promising therapeutic target for inflammatory bowel disease.
eng
MT1-MMP
TSP1
Inflammatory bowel disease
Intussusceptive angiogenesis
Nitric oxide
Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/9631/1/EndothelialMT1%e2%80%90MMPTargetingLimits_2020.pdf
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EndothelialMT1‐MMPTargetingLimits_2020.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/9631/5/EndothelialMT1%e2%80%90MMPTargetingLimits_2020.pdf.txt
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EndothelialMT1‐MMPTargetingLimits_2020.pdf.txt