Matrix regulation of idiopathic pulmonary fibrosis: the role of enzymes

Fibrogenesis & Tissue Repair

Lynne A Murray²  Tomas Mustelin¹  Alan M Carruthers²  Deborah L Clarke² 

[1] MedImmune LLC, Gaithersburg, MD, USA;MedImmune Ltd, Granta Park, Cambridge CB21 6GH, UK

关键词: IPF;    Chronic remodeling;    Matrix;    Fibrosis;   

Others  :  802860
DOI  :  10.1186/1755-1536-6-20

 received in 2013-08-19, accepted in 2013-11-13,  发布年份 2013

【 摘 要 】

Repairing damaged tissues is an essential homeostatic mechanism that enables clearance of dead or damaged cells after injury, and the maintenance of tissue integrity. However, exaggeration of this process in the lung can lead to the development of fibrotic scar tissue. This is characterized by excessive accumulation of extracellular matrix (ECM) components such as fibronectin, proteoglycans, hyaluronic acid, and interstitial collagens. After tissue injury, or a breakdown of tissue integrity, a cascade of events unfolds to maintain normal tissue homeostasis. Inflammatory mediators are released from injured epithelium, leading to both platelet activation and inflammatory cell migration. Inflammatory cells are capable of releasing multiple pro-inflammatory and fibrogenic mediators such as transforming growth factor (TGF)β and interleukin (IL)-13, which can trigger myofibroblast proliferation and recruitment. The myofibroblast population is also expanded as a result of epithelial cells undergoing epithelial-to-mesenchymal transition and of the activation of resident fibroblasts, leading to ECM deposition and tissue remodeling. In the healthy lung, wound healing then proceeds to restore the normal architecture of the lung; however, fibrosis can develop when the wound is severe, the tissue injury persists, or the repair process becomes dysregulated. Understanding the processes regulating aberrant wound healing and the matrix in the chronic fibrotic lung disease idiopathic pulmonary fibrosis (IPF), is key to identifying new treatments for this chronic debilitating disease. This review focuses primarily on the emerging role of enzymes in the lungs of patients with IPF. Elevated expression of a number of enzymes that can directly modulate the ECM has been reported, and recent data indicates that modulating the activity of these enzymes can have a downstream effect on fibrotic tissue remodeling.

【 授权许可】

   
2013 Clarke et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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