Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive fibrosis of the alveolar interstitium. The pathogenesis is thought to involve abnormal reepithelialization and dysregulated remodeling of the extracellular matrix after alveolar injury. There is growing evidence through human and animal studies that oxidative stress plays a role in this dysregulation. Markers of oxidative stress have been identified in the lungs of IPF patients and aberrant antioxidant activity exacerbates pulmonary fibrosis in animal models. In addition, the extracellular matrix is a critical component in regulating cellular homeostasis and appropriate wound healing. Recent investigations support that the matrix is a target of oxidative stress in the lung and IPF. Extracellular matrix degradation products, produced by reactive oxygen species, may promote fibrogenesis by influencing epithelial, mesenchymal, and inflammatory cell activity. The impact of the interactions of oxidative stress and the matrix of the lung remains unclear and may prove to be an important target for new therapies in IPF. Utilizing oxidative enzymes, antioxidants, or the matrix as therapeutic targets to control oxidative stress in IPF will continue be an area of active research and innovative discoveries in the coming years.
Kliment
Corrine R
CR
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Oury
Tim D
TD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
D000975:Antioxidants; D016326:Extracellular Matrix Proteins