Gelatinase B is involved in the in vitro wound repair of human respiratory epithelium

Buisson, Anne-Cécile; Zahm, Jean‐Marie; Polette, Myriam; Pierrot, D.; Bellon, Georges; Puchelle, Édith; Birembaut, Philippe; Tournier, Jean‐Marie

doi:10.1002/(sici)1097-4652(199602)166:2<413::aid-jcp20>3.0.co;2-a

Cited by 106 publications

(93 citation statements)

References 41 publications

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“…MMPs are a family of zinc-and calcium-dependent endopeptidases capable of proteolytically degrading many of the components of the ECM (43), and TIMPs are the endogenous inhibitors of MMPs (44). In pulmonary diseases, MMPs are believed to be associated with wound repair of the human respiratory epithelium (45), while TIMPs are believed to be associated with irreversible pulmonary structure remodeling via myofibroblasts (46). The imbalance of these factors is thought to contribute to the development of interstitial lung diseases (47).…”

Section: Discussionmentioning

confidence: 99%

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Matsuyama

Watanabe

Shirahama

et al. 2005

The Journal of Immunology

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Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen. We previously reported the functional expression of DDR1 on human monocyte-derived macrophages in vitro; however, information regarding its role in diseases is limited. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease, and the lesions contain an abundance of collagen. In this study, we examined DDR1 expression on bronchoalveolar lavage fluid (BALF) cells and investigated its functionality using samples obtained from 28 IPF patients, 13 chronic obstructive pulmonary disease patients, and 14 healthy volunteers. The DDR1 expression level in CD14-positive BALF cells was higher in IPF patients than in chronic obstructive pulmonary disease patients or healthy volunteers. The predominant isoform was DDR1b in the IPF group, while DDR1a was predominant in the other two groups. Using immunohistochemical analysis, we also detected DDR1 expression on infiltrating inflammatory cells in the IPF lesion. In IPF patients, DDR1 activation induced the production of MCP-1, IL-8, MIP-1 α, and matrix metalloproteinase-9 (MMP-9) from CD14-positive BALF cells in a p38 MAPK-dependent manner. In contrast, DDR1 activation of CD14-positive BALF cells in the other groups did not induce the production of these chemokines or MMP-9. These chemokines and MMP-9 contribute to the development of IPF and, therefore, we suggest that DDR1 might be associated with the pathogenesis of IPF in the tissue microenvironment.

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Section: Discussionmentioning

confidence: 99%

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Matsuyama

Watanabe

Shirahama

et al. 2005

The Journal of Immunology

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“…Gelatinase B (MMP-9) expression has been reported to increase in basal cells of wounded primary human bronchial epithelial cell cultures [55][56][57][58] and in distal airway cells after bleomycin injury. 89 However, similar to other groups, 59 we have previously reported that gelatinase B was not expressed in mouse tracheas and human airways at baseline or during injury 23 and once again did not find any gelatinase B expression in these current studies either in ALI cultures or in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Immunofluorescent staining with isotype control antibodies did not detect any nonspecific signal (data not shown). Although some groups have reported gelatinase B (MMP-9) in airway basal epithelial cells, [55][56][57][58] others have not found signal for its protein or mRNA in injured or diseased airway epithelium. 23,59 In our ALI culture repair model, gelatinase B expression was not detected by immunofluorescence in the wounded ALI culture (data not shown).…”

Section: Timp-1 and Matrilysin Co-localize At The Wound Front In Injumentioning

confidence: 99%

Tissue Inhibitor of Metalloproteinase-1 Moderates Airway Re-Epithelialization by Regulating Matrilysin Activity

Chen

McGuire

Hackman

et al. 2008

The American Journal of Pathology

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Obliterative bronchiolitis (OB) is the histopathological finding in chronic lung allograft rejection. Mounting evidence suggests that epithelial damage drives the development of airway fibrosis in OB. Tissue inhibitor of metalloproteinase (TIMP)-1 expression increases in lung allografts and is associated with the onset of allograft rejection. Furthermore, in a mouse model of OB, airway obliteration is reduced in TIMP-1-deficient mice. Matrilysin (matrix metallproteinase-7) is essential for airway epithelial repair and is required for the re-epithelialization of airway wounds by facilitating cell migration; therefore, the goal of this study was to determine whether TIMP-1 inhibits re-epithelialization through matrilysin. We found that TIMP-1 and matrilysin co-localized in the epithelium of human lungs with OB and both co-localized and co-immunoprecipitated in wounded primary airway epithelial cultures. TIMP-1-deficient cultures migrated faster, and epithelial cells spread to a greater extent compared with wild-type cultures. TIMP-1 also inhibited matrilysin-mediated cell migration and spreading in vitro. In vivo, TIMP-1 deficiency enhanced airway re-epithelialization after naphthalene injury. Furthermore, TIMP-1 and matrilysin co-localized in airway epithelial cells adjacent to the wound edge. Our data demonstrate that TIMP-1 interacts with matrix metalloproteinases and regulates matrilysin activity during airway epithelial repair. Furthermore, we speculate that TIMP-1 overexpression restricts airway re-epithelialization by inhibiting matrilysin activity, contributing to a stereotypic injury response that promotes airway fibrosis via bronchiole airway epithelial damage and obliteration. Bronchiolitis obliterans syndrome (BOS) is the manifestation of chronic lung rejection and limits the 5-year survival after lung transplant to less than 50%.1 In comparison, transplantations of other solid organs, such as the heart, pancreas, liver, and kidneys, have 5-year survival rates exceeding 70%.2 Obliterative bronchiolitis (OB) is the histopathological equivalent of BOS and is characterized by small airway fibrosis that contributes to progressive respiratory failure and death.3 Although the pathogenesis of OB is poorly understood, evidence suggests that the primary immunological target in the lung allograft is the airway epithelium. 4 -7 Moreover, aberrant airway re-epithelialization is apparently sufficient for the progression of fibrosis during the allograft rejection process. -13The airway epithelium is an important barrier in the innate defenses of the lung.14 After lung transplantation, persistent allo-dependent (eg, acute rejection) and alloindependent (eg, infection, ischemia) pressures on the airway epithelium necessitate rapid re-epithelialization to prevent further damage that can contribute to inflammation and fibrosis.3 Disturbances in the epithelial barrier are quickly repaired through coordinated processes by which epithelial cells bordering the injury quickly spread over the denuded basement membrane. [15][...

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“…This might be achieved by lowering the O 2 concentration during resuscitation. There is therefore an ongoing debate whether to use 21% or 100% O 2 in neonatal resuscitation (3).Matrix metalloproteinases (MMPs) are involved in the pathogenesis of tissue inflammation and wound healing in lung injury (4,5). The role of oxidative stress and its toxic effects on lipids, as well as on disruption of extracellular matrix through up-regulation of MMPs, is well established (6,7).…”

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confidence: 99%

Resuscitation of Hypoxic Piglets with 100% O2 Increases Pulmonary Metalloproteinases and IL-8

Munkeby

Børke

Björnland³

et al. 2005

Pediatr Res

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We hypothesized that resuscitation with 100% O 2 compared with 21% O 2 is detrimental to pulmonary tissue. The pulmonary injury was assessed by matrix metalloproteinase (MMP) activity, oxidative stress, IL-8, and histology 2.5 h after resuscitation from a hypoxic state. In pulmonary tissue extracts, MMP activity was analyzed by broad matrix-degrading capacity (total MMP) and zymography. MMP-2 mRNA expression was evaluated by quantitative real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) assay, and IL-8 was analyzed by ELISA technique. In bronchoalveolar lavage (BAL) fluid, MMPs were analyzed by zymography. In pulmonary tissue, pro-and active MMP-2 levels were increased in piglets that were resuscitated with 100% O 2 compared with 21% O 2 . Pro-MMP-9, total MMP activity, and MMP-2 mRNA levels were significantly increased in resuscitated piglets compared with baseline. Net gelatinolytic activity increased in submucosa and blood vessels after 100% O 2 and only in the blood vessels after 21% O 2 . Compared with baseline, ORAC values were considerably lowered in the resuscitated piglets and significantly reduced in the 100% O 2 versus 21% O 2 group. In BAL fluid, both pro-MMP-9 and pro-MMP-2 increased 2-fold in the 100% O 2 group compared with 21% O 2 . Moreover, IL-8 concentration increased significantly in piglets that were resuscitated with 100% O 2 compared with 21% O 2 , suggesting a marked proinflammatory response in the pulmonary tissue. Altogether, these data strongly suggest that caution must be taken when applying pure O 2 to the newborn infant. Traditionally, asphyxiated newborn infants have been resuscitated with 100% O 2 . This recommendation is based mainly on precedent rather than sound evidence. Hyperoxia leads to generation of O 2 free radicals, which have a role in reperfusion injury after asphyxia (1). Naturally, the lung is exposed directly to the highest partial pressure of inspired O 2 , and pulmonary damage, as a result of O 2 exposure, is a serious clinical complication in infants who require high levels of O 2 as treatment (2). It is important not only to provide adequate O 2 consumption in organs but also to prevent further tissue damage during resuscitation caused by reoxygenation injury or O 2 toxicity. This might be achieved by lowering the O 2 concentration during resuscitation. There is therefore an ongoing debate whether to use 21% or 100% O 2 in neonatal resuscitation (3).Matrix metalloproteinases (MMPs) are involved in the pathogenesis of tissue inflammation and wound healing in lung injury (4,5). The role of oxidative stress and its toxic effects on lipids, as well as on disruption of extracellular matrix through up-regulation of MMPs, is well established (6,7). Reduced Received November 19, 2004; accepted February 1, 2005

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Gelatinase B is involved in the in vitro wound repair of human respiratory epithelium

Cited by 106 publications

References 41 publications

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Activation of Discoidin Domain Receptor 1 on CD14-Positive Bronchoalveolar Lavage Fluid Cells Induces Chemokine Production in Idiopathic Pulmonary Fibrosis

Tissue Inhibitor of Metalloproteinase-1 Moderates Airway Re-Epithelialization by Regulating Matrilysin Activity

Resuscitation of Hypoxic Piglets with 100% O2 Increases Pulmonary Metalloproteinases and IL-8

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