Lung Tissue Mechanics and Extracellular Matrix  Remodeling in Acute Lung Injury

Rocco, Patrícia Rieken Macêdo; Negri, Eva; Kurtz, Pedro M.; Vasconcellos, Fernanda P.; Silva, Gabriela H.; Capelozzi, Vera Luíza; Romero, P.; Zin, Walter A.

doi:10.1164/ajrccm.164.6.2007062

Cited by 154 publications

(134 citation statements)

References 34 publications

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“…Using an i.p. injection of paraquat model of lung injury in rats, investigators have demonstrated that altered tissue mechanics associated with markers of ECM remodelling are detected as early as 24 h after injury [65]. In another animal study, pulmonary mechanics were assessed in mice with lung injury induced by administration of LPS (either 125 mg i.p.…”

Section: Mmps In Repair Of the Alveolar Epithelial-endothelial Unitmentioning

confidence: 99%

Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair

Davey¹,

McAuley

O'Kane

2011

European Respiratory Journal

193

137

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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) comprise a spectrum of acute inflammatory pulmonary oedema resulting in refractory hypoxaemia in the absence of an underlying cardiogenic cause. There are multiple pulmonary and extrapulmonary causes and ALI/ARDS patients are a clinically heterogeneous group with associated high morbidity and mortality.Inflammatory injury to the alveolar epithelial and endothelial capillary membrane is a central event in the pathogenesis of ALI/ARDS, and involves degradation of the basement membrane. Matrix metalloproteinases (MMPs) have been implicated in a wide variety of pulmonary pathologies and are capable of degrading all components of the extracellular matrix including the basement membrane and key non-matrix mediators of lung injury such as chemokines and cell surface receptors.While many studies implicate MMPs in the injurious process, there are significant gaps in our knowledge of the role of specific proteases at different phases of injury and repair. This article examines the role of MMPs in injury and repair of the alveolar epithelial-endothelial capillary barrier and discusses the potential for MMP modulation in the prevention and treatment of ALI. The need for further mechanistic and in vivo studies to inform appropriate subsequent clinical trials of MMP modulation will be highlighted. KEYWORDS: Acute lung injury, acute respiratory distress syndrome, extracellular matrix, inflammation, matrix metalloproteinases, repair A cute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are part of a disease spectrum associated with high mortality and considerable morbidity. The most recent diagnostic criteria for ALI/ARDS, developed by the 1994 American-European Consensus Conference Committee [1], are based on the gross clinico-radiological findings; acute onset, bilateral infiltrates on chest radiography, absence of left ventricular failure and the ratio of arterial oxygen tension (Pa,O 2 , expressed in mmHg) to inspired oxygen fraction (FI,O 2 ) measuring ,200 (ARDS) or ,300 (ALI) [2][3][4]. However, ALI/ARDS patients are clinically heterogeneous and this definition does not take into account the underlying aetiology or severity of illness reflected by failure of other organ systems [2]. Irrespective of aetiology, the pathogenesis of ALI/ARDS consists of an excessive and inappropriate inflammatory response to a range of pulmonary or extrapulmonary insults, resulting in damage to the alveolar epithelial-endothelial capillary barrier [3,4]. Clinically, this manifests as refractory hypoxaemia and decreased pulmonary compliance. Pathologically, three phases are recognised: an initial acute inflammatory or exudative phase characterised by

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Section: Mmps In Repair Of the Alveolar Epithelial-endothelial Unitmentioning

confidence: 99%

Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair

Davey¹,

McAuley

O'Kane

2011

European Respiratory Journal

193

137

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Section: Discussionmentioning

confidence: 99%

“…Exposure to paraquat generates physiological characteristics of acute lung injury (ALI) (Rocco et al, 2001). Collagen and other elastic components are increased in the ALI process due to a fibroelastosis process initiated early in the first 24 h of lesion evolution (Rocco et al, 2001). Exposure to paraquat can significantly induce the expression of connective tissue growth factor, which results in a process of pulmonary fibrosis (Huang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Changes in the Respiratory System of Rats Exposed to the Herbicide Paraquat

2017

International Journal of Research Studies in Biosciences

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“…The components of the ECM can be divided into four broad categories: collagen, non-collagenous glycoproteins (such as fibronectin and laminin), glycosaminoglycans and proteoglycans (PTGs), and elastic fibers (48,51,52). Cells continuously remodel their microenvironment by changing the components and structure of the ECM (52,53).…”

Section: Stretch-induced Extracellular Matrix Expressionmentioning

confidence: 99%

Understanding the mechanisms of lung mechanical stress

Garcia

Prota

Morales

et al. 2006

Braz J Med Biol Res

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Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical forcerelated disorders.

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Lung Tissue Mechanics and Extracellular Matrix Remodeling in Acute Lung Injury

Abstract: elastance; collagen fibers; elastin; paraquat

Cited by 154 publications

References 34 publications

Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair

Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair

Changes in the Respiratory System of Rats Exposed to the Herbicide Paraquat

Understanding the mechanisms of lung mechanical stress

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