Differential expression of matrix metalloproteinases and their inhibitors in human and mouse lung development

Ryu, Julie; Vicencio, Alfin G.; Yeager, Michael E.; Kashgarian, Michael; Haddad, Gabriel G.; Eickelberg, Oliver

doi:10.1160/th04-10-0656

Cited by 43 publications

(33 citation statements)

References 45 publications

(48 reference statements)

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“…Expression studies provide support for the expression of these toothrelated genes in other biomineralized tissues (22,33,34) (table S1). Similarly, MMP20 is located in one of the MMP gene clusters with several other matrix metalloproteinase genes, and its coexpression in nondental tissues (e.g., lung and large intestine) (21,35,36) with other MMPs may be attributed, in part, to gene expression neighborhoods.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a single loss of mineralized teeth in the common avian ancestor

Meredith

Zhang

Gilbert

et al. 2014

Science

103

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Edentulism, the absence of teeth, has evolved convergently among vertebrates, including birds, turtles, and several lineages of mammals. Instead of teeth, modern birds (Neornithes) use a horny beak (rhamphotheca) and a muscular gizzard to acquire and process food. We performed comparative genomic analyses representing lineages of nearly all extant bird orders and recovered shared, inactivating mutations within genes expressed in both the enamel and dentin of teeth of other vertebrate species, indicating that the common ancestor of modern birds lacked mineralized teeth. We estimate that tooth loss, or at least the loss of enamel caps that provide the outer layer of mineralized teeth, occurred about 116 million years ago.

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Section: Discussionmentioning

confidence: 99%

Evidence for a single loss of mineralized teeth in the common avian ancestor

Meredith

Zhang

Gilbert

et al. 2014

Science

103

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“…The fetal lung has a dominant proteolytic profile with high MMP-2, whereas the adult lung exhibits a more antiproteolytic profile with decreased MMP-2 (14). Thus, MMPs appear to play different roles in neonatal and adult hypoxia-induced pulmonary arterial remodeling.…”

Section: Mmp2mentioning

confidence: 99%

“…Other investigators (14,33) have evaluated MMP-2 in the developing lung during hypoxia. Gebb et al (33) showed that MMP-2 by zymography was lower at 3% compared with 21% O 2 in fetal rat lung explants despite no change in MMP-2 mRNA levels, indicating that hypoxia suppressed MMP-2 …”

Section: Mmp2mentioning

confidence: 99%

“…The gelatinases (MMP-2 and MMP-9) degrade collagen more efficiently than other MMPs (12). MMP-2 is the predominant gelatinase in the developing lung (13), and the fetal human lung has a proteolytic profile with higher MMP-2 compared with the adult lung (14). Pro-MMP-2 (72 kD) is converted to an active form (66 kD) that in turn cleaves many substrates, including collagen, fibronectin, and elastin (15).…”

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confidence: 99%

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Role of Matrix Metalloproteinase-2 in Newborn Mouse Lungs under Hypoxic Conditions

et al. 2008

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Hypoxia impairs normal neonatal pulmonary artery remodeling and alveolar development. Matrix metalloproteinase-2 (MMP-2), which regulates collagen breakdown, is important during development. Our objective was to test the hypothesis that hypoxia attenuates the normal postnatal increase in MMP-2 and evaluate alveolar development and pulmonary arterial remodeling in Mmp2 Ϫ/Ϫ mice. C57BL/6 wild-type (WT), Mmp2 ϩ/Ϫ , Mmp2 Ϫ/Ϫ , and MMP-inhibited (with doxycycline) mice were exposed to hypoxia (12% O 2 ) or air from birth to 2 wk of age. Pulmonary arterial remodeling, alveolar development, and vascular collagen and elastin were evaluated. MMP-2 was estimated by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, and zymography. We observed that 1) in WT mice, hypoxia led to thicker-walled pulmonary arteries and impaired alveolarization, accompanied by decreased MMP-2 and increased tissue inhibitor of metalloproteinases-2 (TIMP-2); 2) Mmp2 Ϫ/Ϫ mice in air had thicker-walled arteries, impaired alveolarization, and increased perivascular collagen and elastin compared with WT; 3) hypoxia further inhibited alveolarization but did not alter arterial thickening in Mmp2 Ϫ/Ϫ mice. Mmp2 ϩ/Ϫ and MMP-inhibited mice also had thicker-walled arteries than WT in air, but alveolarization was not different. We conclude that hypoxia reduces the postnatal MMP-2 increase in the lung, which may contribute to abnormal pulmonary arterial remodeling and impaired alveolarization. C hronic hypoxia leads to abnormal pulmonary arterial remodeling with excessive collagen and elastin deposition (1), similar to that observed in persistent pulmonary hypertension of the newborn (2), bronchopulmonary dysplasia (BPD) (3), and congenital heart disease (4,5). Chronic hypoxia also permanently inhibits alveolar development (6,7), which normally begins in late gestation in humans and postnatally in mice (8,9).The hypoxia-induced effects on pulmonary arterial remodeling and alveolarization suggest that hypoxia alters extracellular matrix (ECM) turnover. Matrix metalloproteinases (MMPs) regulated by tissue inhibitors of metalloproteinases (TIMPs) regulate ECM turnover (10), and only specific MMPs can initiate collagen breakdown (11). The gelatinases (MMP-2 and MMP-9) degrade collagen more efficiently than other MMPs (12). MMP-2 is the predominant gelatinase in the developing lung (13), and the fetal human lung has a proteolytic profile with higher MMP-2 compared with the adult lung (14). Pro-MMP-2 (72 kD) is converted to an active form (66 kD) that in turn cleaves many substrates, including collagen, fibronectin, and elastin (15). The other gelatinase, MMP-9, is chiefly expressed by inflammatory and epithelial cells (16) and not by pulmonary arteries (17). MMP-2 activity is primarily regulated at the level of activation of pro-MMP-2 by TIMP-2 and MMP-14 (18 -20). TIMP-2 potentiates MMP-2 activation at low concentrations and inhibits it at higher concentrations (21).In the current study, we focuse...

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“…Remodelling of the extracellular matrix is a key feature of postnatal alveolar septation [24] with various matrix metalloproteinases (MMPs), zinc-dependent endopeptidases, involved [25,26]. Gelatinase A (MMP-2), gelatinase B (MMP-9) and macrophage metalloelastase (MMP-12) play a key role in emphysema development and progression [27][28][29].…”

mentioning

confidence: 99%

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages

Seifart

Muyal

Plagens

et al. 2011

European Respiratory Journal

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All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs).Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 mg?kg -1 body weight)versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA-or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1 + :ED2 + macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1b, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-a, nuclear factor-kB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.

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Differential expression of matrix metalloproteinases and their inhibitors in human and mouse lung development

Cited by 43 publications

References 45 publications

Evidence for a single loss of mineralized teeth in the common avian ancestor

Evidence for a single loss of mineralized teeth in the common avian ancestor

Role of Matrix Metalloproteinase-2 in Newborn Mouse Lungs under Hypoxic Conditions

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages

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