The multifaceted roles of the matrikine Pro-Gly-Pro in pulmonary health and disease
File(s)
Published version
Author(s)
Patel, Dhiren F
Snelgrove, Robert J
Type
Journal Article
Abstract
Matrikines are bioactive fragments of the extracellular matrix (ECM) that are fundamental in regulating a diverse array of physiological processes. The tripeptide Proline-Glycine-Proline (PGP) is a collagen-derived matrikine that has classically been described as a neutrophil chemoattractant. In this article, we describe our current understanding of the pathways that generate, degrade and modify PGP to dictate its bioavailability and stability. Additionally, we discuss our expanding appreciation of the capacity of PGP to regulate diverse cell types and biological processes, independent of its activity on neutrophils, including a putative role in wound repair. We argue that PGP functions as a primitive and conserved damage-associated molecular pattern, which is generated during infection or injury and subsequently acts to shape ensuing inflammatory and repair processes. As a fragment of the ECM that accumulates at the epicentre of the action, PGP is perfectly positioned to focus neutrophils to the exact site required and direct a localised repair response. However, it is essential that PGP is efficiently degraded, as if this matrikine is allowed to persist then pathology can ensue. Accordingly, we discuss how this pathway is subverted in chronic lung diseases giving rise to persistent inflammation and pathological tissue remodelling.
Date Issued
2018-06-30
Date Acceptance
2018-06-08
Citation
European Respiratory Review, 2018, 27 (148)
ISSN
0905-9180
Publisher
European Respiratory Society
Journal / Book Title
European Respiratory Review
Volume
27
Issue
148
Copyright Statement
© 2018 ERS. ERR articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0 (https://creativecommons.org/licenses/by-nc/4.0/).
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000437470300011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
209458/Z/17/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
PROLINE-GLYCINE-PROLINE
LEUKOTRIENE A(4) HYDROLASE
I-CONVERTING-ENZYME
NEUTROPHILIC INFLAMMATION
LUNG EMPHYSEMA
SEVERE ASTHMA
PEPTIDE
CHEMOATTRACTANT
CARBOCISTEINE
CORNEA
Publication Status
Published
Article Number
180017
Date Publish Online
2018-06-27