Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases during normal human pulmonary development

Masumoto, Kouji; Rooij, Jessica D. de; Suita, Sachiyo; Rottier, Robbert J.; Tibboel, Dick; Krijger, Ronald R. de

doi:10.1111/j.1365-2559.2005.02228.x

Cited by 31 publications

(27 citation statements)

References 34 publications

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“…It consists of a network of proteases/antiproteases including MMP9, MMP12, TIMP1, MMP8, secretory leukocyte peptidase inhibitor, and ADAM metallopeptidase with thrombospondin type 1 motif, 5 (ADAMTS5). The function of MMP9, also called gelatinase B, has been studied in lung development and lung inflammatory diseases such as BPD (3,10). Levels of MMP9 are increased in animal models of BPD (11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

et al. 2015

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Background: Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. Methods: Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. results: In fully treated animals (LPS + MV + 60% O 2 ) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/ wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. conclusion: MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.

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Section: Discussionmentioning

confidence: 99%

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

et al. 2015

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“…TGF-␤ regulates the secretion of some matrix-metabolizing enzymes: the MMPs and their cognate inhibitors, TIMPs. Throughout the canalicular, saccular, and alveolar phases of normal lung development, MMP-1, MMP-2, MMP-9, and TIMP-2 are strongly expressed in humans (29) and mice (44), and during normal development, MMP-9 expression peaks during alveolarization (5), indicating the importance of matrix remodeling in this process. In our study, we have illustrated that TGF-␤ stimulation dramatically elevates levels of mRNA encoding TIMP-1 in fibroblasts cultured in 85% O 2 , compared with fibroblasts cultured in 21% O 2 , whereas mRNA levels of MMP-1 and MMP-2 were either unaffected or decreased.…”

Section: Discussionmentioning

confidence: 99%

Hyperoxia modulates TGF-β/BMP signaling in a mouse model of bronchopulmonary dysplasia

Alejandre-Alcázar

Kwapiszewska²,

Reiss³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

207

128

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-Prematurely born infants who require oxygen therapy often develop bronchopulmonary dysplasia (BPD), a debilitating disorder characterized by pronounced alveolar hypoplasia. Hyperoxic injury is believed to disrupt critical signaling pathways that direct lung development, causing BPD. We investigated the effects of normobaric hyperoxia on transforming growth factor (TGF)-␤ and bone morphogenetic protein (BMP) signaling in neonatal C57BL/6J mice exposed to 21% or 85% O2 between postnatal days P1 and P28. Growth and respiratory compliance were significantly impaired in pups exposed to 85% O2, and these pups also exhibited a pronounced arrest of alveolarization, accompanied by dysregulated expression and localization of both receptor (ALK-1, ALK-3, ALK-6, and the TGF-␤ type II receptor) and Smad (Smads 1, 3, and 4) proteins. TGF-␤ signaling was potentiated, whereas BMP signaling was impaired both in the lungs of pups exposed to 85% O2 as well as in MLE-12 mouse lung epithelial cells and NIH/3T3 and primary lung fibroblasts cultured in 85% O2. After exposure to 85% O2, primary alveolar type II cells were more susceptible to TGF-␤-induced apoptosis, whereas primary pulmonary artery smooth muscle cells were unaffected. Exposure of primary lung fibroblasts to 85% O2 significantly enhanced the TGF-␤-stimulated production of the ␣1 subunit of type I collagen (I␣1), tissue inhibitor of metalloproteinase-1, tropoelastin, and tenascin-C. These data demonstrated that hyperoxia significantly affects TGF-␤/BMP signaling in the lung, including processes central to septation and, hence, alveolarization. The amenability of these pathways to genetic and pharmacological manipulation may provide alternative avenues for the management of BPD.

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“…In humans, MMPs, particularly MMP-1, -2 and -9, are important during the vascular remodelling that is a normal part of lung development [112]. Although MMPs have been shown to have a role in vascular remodelling in a variety of animal models of pulmonary hypertension, including hypoxia and monocrotaline induced pulmonary hypertension, we will confine ourselves here to the vascular remodelling seen in COPD, or to relevant data gleaned from isolated cell experiments.…”

Section: Mmps In Vascular Remodelling Associated With Pulmonary Hypermentioning

confidence: 99%

Matrix metalloproteinases in COPD

Churg

Zhou²,

Wright³

2011

European Respiratory Journal

237

116

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There is considerable evidence that matrix metalloproteinases (MMPs) are up-and/or downregulated in chronic obstructive pulmonary disease (COPD), particularly in emphysema, in which they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD. In cigarette smoke-induced animal models of emphysema, MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs, evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodelling, smokeinduced pulmonary hypertension and chronic bronchitis, but MMP-12 participates in experimental small airway modelling. To date, the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodelling, but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.

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Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases during normal human pulmonary development

Cited by 31 publications

References 34 publications

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

Hyperoxia modulates TGF-β/BMP signaling in a mouse model of bronchopulmonary dysplasia

Matrix metalloproteinases in COPD

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