Altmetric

Systems-genetics identifies a macrophage cholesterol network associated with physiological wound healing

File Description SizeFormat 
Bagnati_Systems genetics identifies_JCI insight.pdfPublished version6.35 MBAdobe PDFView/Open
Title: Systems-genetics identifies a macrophage cholesterol network associated with physiological wound healing
Authors: Bagnati, M
Moreno-Moral, A
Ko, J-H
Nicod, J
Harmston, N
Imprialou, M
Game, L
Gil, J
Petretto, E
Behmoaras, J
Item Type: Journal Article
Abstract: Among other cells, macrophages regulate the inflammatory and reparative phases during wound healing but genetic determinants and detailed molecular pathways that modulate these processes are not fully elucidated. Here, we took advantage of normal variation in wound healing in 1,378 genetically outbred mice, and carried out macrophage RNA-sequencing profiling of mice with extreme wound healing phenotypes (i.e., slow and fast healers, n = 146 in total). The resulting macrophage coexpression networks were genetically mapped and led to the identification of a unique module under strong trans-acting genetic control by the Runx2 locus. This macrophage-mediated healing network was specifically enriched for cholesterol and fatty acid biosynthetic processes. Pharmacological blockage of fatty acid synthesis with cerulenin resulted in delayed wound healing in vivo, and increased macrophage infiltration in the wounded skin, suggesting the persistence of an unresolved inflammation. We show how naturally occurring sequence variation controls transcriptional networks in macrophages, which in turn regulate specific metabolic pathways that could be targeted in wound healing.
Issue Date: 24-Jan-2019
Date of Acceptance: 18-Dec-2018
URI: http://hdl.handle.net/10044/1/66898
DOI: https://dx.doi.org/10.1172/jci.insight.125736
ISSN: 2379-3708
Publisher: American Society for Clinical Investigation
Journal / Book Title: JCI insight
Volume: 4
Issue: 2
Copyright Statement: © 2019, American Society for Clinical Investigation. By permission of ASCI.
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/M004716/1
MR/N01121X/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
GENOME-WIDE ASSOCIATION
QUANTITATIVE TRAIT LOCI
COMPLEX TRAITS
BONE-MARROW
INFLAMMATION
EXPRESSION
RUNX2
LINK
REGENERATION
HOMEOSTASIS
Cholesterol
Dermatology
Inflammation
Macrophages
Publication Status: Published
Article Number: e125736
Appears in Collections:Clinical Sciences
Molecular Sciences
Department of Medicine
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx