p75NTR-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte–endothelial crosstalk in diabetes after limb ischaemia

Andrea Caporali (), Marco Meloni, Audrey Nailor, Tijana Mitić, Saran Shantikumar, Federica Riu, Graciela B. Sala-Newby, Lorraine Rose, Marie Besnier, Rajesh Katare, Christine Voellenkle, Paul Verkade, Fabio Martelli, Paolo Madeddu and Costanza Emanueli
Additional contact information
Andrea Caporali: School of Clinical Sciences, Bristol Heart Institute
Marco Meloni: School of Clinical Sciences, Bristol Heart Institute
Audrey Nailor: School of Clinical Sciences, Bristol Heart Institute
Tijana Mitić: School of Clinical Sciences, Bristol Heart Institute
Saran Shantikumar: School of Clinical Sciences, Bristol Heart Institute
Federica Riu: School of Clinical Sciences, Bristol Heart Institute
Graciela B. Sala-Newby: School of Clinical Sciences, Bristol Heart Institute
Lorraine Rose: University/British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh
Marie Besnier: School of Clinical Sciences, Bristol Heart Institute
Rajesh Katare: School of Clinical Sciences, Bristol Heart Institute
Christine Voellenkle: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato
Paul Verkade: Wolfson Bioimaging Facility, University of Bristol
Fabio Martelli: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato
Paolo Madeddu: School of Clinical Sciences, Bristol Heart Institute
Costanza Emanueli: School of Clinical Sciences, Bristol Heart Institute

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract The communication between vascular endothelial cells (ECs) and pericytes in the microvasculature is fundamental for vascular growth and homeostasis; however, these processes are disrupted by diabetes. Here we show that modulation of p75NTR expression in ECs exposed to high glucose activates transcription of miR-503, which negatively affects pericyte function. p75NTR activates NF-κB to bind the miR-503 promoter and upregulate miR-503 expression in ECs. NF-κB further induces activation of Rho kinase and shedding of endothelial microparticles carrying miR-503, which transfer miR-503 from ECs to vascular pericytes. The integrin-mediated uptake of miR-503 in the recipient pericytes reduces expression of EFNB2 and VEGFA, resulting in impaired migration and proliferation. We confirm operation of the above mechanisms in mouse models of diabetes, in which EC-derived miR-503 reduces pericyte coverage of capillaries, increased permeability and impaired post-ischaemic angiogenesis in limb muscles. Collectively, our data demonstrate that miR-503 regulates pericyte–endothelial crosstalk in microvascular diabetic complications.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9024 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9024

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9024

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().