Overexpression of Alveolar Macrophage Gelatinase B (MMP-9) in Patients with Idiopathic Pulmonary Fibrosis

Lemjabbar, Hassan; Gosset, Philippe; Lechapt‐Zalcman, Emmanuèle; Franco-Montoya, Marie-Laure; Wallaert, B.; Harf, Alain; Lafuma, C.

doi:10.1165/ajrcmb.20.5.3260

Cited by 122 publications

(88 citation statements)

References 39 publications

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“…It has been suggested that the tissue phenotype of fibrosis (primarily the exaggerated extracellular matrix deposition) results from dysregulation of the synthesis and degradation of extracellular matrix proteins-a process that could involve several members of the MMP family. Thus, MMP-1 (collagenase-1 that degrades fibrillar collagens) as well as MMP-2 and MMP-9 (gelatinases A and B, which have a broad range of substrates including type IV collagens from basement membranes) have previously been reported to be up-regulated in human pulmonary fibrosis and animal models of pulmonary fibrosis (17)(18)(19). In our data set, MMP-1, MMP-2, and MMP-9 were significantly higher in UIP lungs.…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans

Zuo

Kaminski

Eugui

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

556

487

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Pulmonary fibrosis is a progressive and largely untreatable group of disorders that affects up to 100,000 people on any given day in the United States. To elucidate the molecular mechanisms that lead to end-stage human pulmonary fibrosis we analyzed samples from patients with histologically proven pulmonary fibrosis (usual interstitial pneumonia) by using oligonucleotide microarrays. Gene expression patterns clearly distinguished normal from fibrotic lungs. Many of the genes that were significantly increased in fibrotic lungs encoded proteins associated with extracellular matrix formation and degradation and proteins expressed in smooth muscle. Using a combined set of scoring systems we determined that matrilysin (matrix metalloproteinase 7), a metalloprotease not previously associated with pulmonary fibrosis, was the most informative increased gene in our data set. Immunohistochemisry demonstrated increased expression of matrilysin protein in fibrotic lungs. Furthermore, matrilysin knockout mice were dramatically protected from pulmonary fibrosis in response to intratracheal bleomycin. Our results identify matrilysin as a mediator of pulmonary fibrosis and a potential therapeutic target. They also illustrate the power of global gene expression analysis of human tissue samples to identify molecular pathways involved in clinical disease.usual interstitial pneumonia ͉ microarray analysis ͉ informative genes ͉ bleomycin ͉ matrix metalloproteases

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Section: Discussionmentioning

confidence: 99%

Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans

Zuo

Kaminski

Eugui

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

556

487

View full text Add to dashboard Cite

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“…TIMP-1 expression is correlated with stages of disease progression and may prevent MMPinduced extracellular matrix degradation, and, as a consequence, may participate in the accumulation of extracellular matrix. MMP detection could be proposed as a prognosis factor in lung fibrosis as described for MMP-9 (Lemjabbar et al, 1999).…”

Section: Lung Fibrosismentioning

confidence: 99%

“…MMP-2 is localized in structural cells like regenerated alveolar epithelial, bronchial epithelial cells and fibroblasts. In lung fibrosis, MMP-2 could play a role in the regeneration of alveolar epithelial cells Lemjabbar et al, 1999;Manoury et al, 2005;Scabilloni et al, 2005). The expression of the two gelatinases (MMP-2 and MMP-9) at different stages of fibrosis suggests that MMP-9 could be rather linked to inflammation-induced tissue remodeling, while MMP-2 may be associated with an impaired tissue remodeling leading to pathological collagen deposition and interstitial fibrosis.…”

mentioning

confidence: 99%

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Guéders

Foidart

Noël

et al. 2006

European Journal of Pharmacology

279

224

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In healthy lung, Matrix Metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), are produced in the respiratory tract by a panel of different structural cells. These activities are mandatory for many physiological processes including development, wound healing and cell trafficking. Deregulation of proteolytic-antiproteolytic network and inappropriate secretion of various MMPs by stimulated structural or inflammatory cells is thought to take part to pathophysiology of numerous lung diseases including asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis and lung cancer. Cytokines and growth factors are involved in these inflammatory processes and some of those mediators interact directly with MMPs and TIMPs leading either to a regulation of their expression or changes in their biological activities by proteolytic cleavage. In turn, cytokines and growth factors modulate secretion of MMPs establishing a complex network of reciprocal interactions. Every MMP seem to play a rather specific role and some variations of their expression are observed in different lung diseases. The precise role of these enzymes and their inhibitors is now studied in depth as they could represent relevant therapeutic targets for many diseases. Indeed, MMP inhibition can lead either to a decrease of the intensity of a pathological process or, in the contrary for some of them, to an increase of disease severity. In this review, we focus on the role played by MMPs and TIMPs in asthma and we provide an overview of their potential roles in COPD, lung fibrosis and lung cancer, with a special emphasis on loops including MMPs and cytokines and growth factors relevant in these diseases.Keywords: Matrix metalloproteinase; Tissue inhibitor of MMP; Asthma; Cytokine; Growth factors Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)Matrix metalloproteinases (MMPs), or matrixins, belong to the metzincin superfamily of metalloproteinases, also including astacins, ADAMs (a protein with a disintegrin and metallopro-tease domain) and ADAM-TS proteases (ADAM with a thrombospondin-like motif) (Sternlicht and Werb, 2001;Folgueras et al., 2004;Handsley and Edwards, 2005;Noel et al., 2004). MMPs are proteolytic enzymes believed to be implicated in many physiological and pathological processes including embryonic development, morphogenesis, reproductive processes, bone remodeling, wound healing, cancer, arthritis, atherosclerosis, MMPs are zinc and calciumdependent enzymes being able to degrade virtually all extracellular matrix components. This can modulate cell behaviour by creating influential cellular environment (Shapiro, 1998). The extracellular matrix is a complex network of molecules including collagens, fibronectin, laminin, entactin/ nidogen and heparan sulfate proteoglycans (Mott and Werb, 2004). The extracellular matrix is a mechanical support for cells but also acts as a reservoir for cytokines and growth factors (vascular endothelial ...

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“…A previous study revealed that latent gelatinase B, as well an active form, was significantly increased in culture medium (24 hrs) of activated alveolar macrophages from bronchoalveolar lavage of patients with idiopathic pulmonary fibrosis 30. Thus, it is reasonable to hypothesize that surfactant induced a macrophage‐mediated gelatinolytic activity in our coculture model with myofibroblasts since the addition of surfactant caused disruption of the integrity of the myofibroblast monolayer.…”

Section: Discussionmentioning

confidence: 76%

Exogenous pulmonary surfactant prevents the development of intra‐abdominal adhesions in rats

Schanaider

Cotta-Pereira

Silva

et al. 2016

J Cellular Molecular Medi

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Intra‐abdominal adhesions are major post‐operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post‐operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L‐S and GE‐S, respectively). Intra‐abdominal adhesions, collagen fibre content, metalloproteinase (MMP)‐9, expression of growth factors (TGF‐β, KGF and VEGF), type III procollagen (PCIII) and pro‐caspase 3, as well as isolectin B4 and ED1‐positive cells expressing MMP‐9, were evaluated. Groups treated with surfactant (GE‐S and L‐S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE‐S compared to GE animals (P < 0.001). In situ and gelatin zymography analysis showed higher MMP‐9 expression and activity in the GE‐S group compared to the GE group (P < 0.05). ED1‐positive cell counts were significantly higher in the GE‐S group (P < 0.001) than in the GE group. Virtually all cells positive for ED1 were MMP‐9+. Double‐labelling of MMP‐9 with IB4 showed no significant differences between GE‐S and GE groups. TGF‐β, KGF, PCIII and pro‐caspase‐3 mRNA expression decreased significantly in GE‐S compared to GE animals (P < 0.05). Surfactant administration also reduced apoptosis in the GE‐S group. These findings suggest that surfactant reduces the intra‐abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra‐abdominal adhesions with surfactant and to endorse its putative mechanism of action.

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Overexpression of Alveolar Macrophage Gelatinase B (MMP-9) in Patients with Idiopathic Pulmonary Fibrosis

Cited by 122 publications

References 39 publications

Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans

Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

Exogenous pulmonary surfactant prevents the development of intra‐abdominal adhesions in rats

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