Inflammation, Repair and Development Section, National Heart and Lung Institute, Imperial College London, London, UK.
Eur Respir Rev. 2018 Jun 27;27(148). doi: 10.1183/16000617.0017-2018. Print 2018 Jun 30.
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.
基质细胞衍生因子是细胞外基质（ECM）的生物活性片段，对于调节多种生理过程至关重要。三肽脯氨酸-甘氨酸-脯氨酸（PGP）是一种源自胶原蛋白的基质细胞衍生因子，经典地被描述为一种中性粒细胞趋化因子。在本文中，我们描述了我们目前对产生、降解和修饰 PGP 以决定其生物利用度和稳定性的途径的理解。此外，我们还讨论了我们对 PGP 调节多种细胞类型和生物学过程的能力的不断认识，包括其在伤口修复中的潜在作用，这种作用与其在中性粒细胞上的活性无关。我们认为，PGP 作为一种原始且保守的损伤相关分子模式发挥作用，它在感染或损伤期间产生，并随后作用于塑造随后的炎症和修复过程。作为 ECM 的一个片段，PGP 在作用的中心积累，使中性粒细胞能够准确地集中到所需的位置，并引导局部修复反应。然而，PGP 必须被有效地降解，因为如果这种基质细胞衍生因子持续存在，那么就可能导致病理发生。因此，我们讨论了这条途径在慢性肺部疾病中是如何被颠覆的，导致持续的炎症和病理性组织重塑。
