Role of Matrix Metalloproteinases in Angiogenesis and Its Implications in Asthma

Bajbouj, Khuloud; Ramakrishnan, Rakhee K.; Hamid, Qutayba

doi:10.1155/2021/6645072

Cited by 29 publications

(32 citation statements)

References 100 publications

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“…Myeloperoxidase (MPO), contained in neutrophil primary/azurophilic granules, plays a pivotal role in ROS production [72,73] and NET formation [74,75]. Matrix metalloproteinase-9 (MMP-9) plays a key role in the development of airway inflammation [76][77][78][79] and facilitates angiogenesis in asthma [80]. Circulating [81] and BAL levels of CXCL8 [82] are increased in asthmatics.…”

Section: Plasma Levels Of Neutrophil-derived Mediatorsmentioning

confidence: 99%

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

et al. 2021

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Neutrophils (PMNs) contain and release a powerful arsenal of mediators, including several granular enzymes, reactive oxygen species (ROS) and neutrophil extracellular traps (NETs). Although airway neutrophilia is associated with severity, poor response to glucocorticoids and exacerbations, the pathophysiological role of neutrophils in asthma remains poorly understood. Twenty-four patients with asthma and 22 healthy controls (HCs) were prospectively recruited. Highly purified peripheral blood neutrophils (> 99%) were evaluated for ROS production and activation status upon stimulation with lipopolysaccharide (LPS), N-formylmethionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). Plasma levels of myeloperoxidase (MPO), CXCL8, matrix metalloproteinase-9 (MMP-9), granulocyte–monocyte colony-stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF-A) were measured by ELISA. Plasma concentrations of citrullinated histone H3 (CitH3) and circulating free DNA (dsDNA) were evaluated as NET biomarkers. Activated PMNs from asthmatics displayed reduced ROS production and activation status compared to HCs. Plasma levels of MPO, MMP-9 and CXCL8 were increased in asthmatics compared to HCs. CitH3 and dsDNA plasma levels were increased in asthmatics compared to controls and the CitH3 concentrations were inversely correlated to the % decrease in FEV1/FVC in asthmatics. These findings indicate that neutrophils and their mediators could have an active role in asthma pathophysiology.

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Section: Plasma Levels Of Neutrophil-derived Mediatorsmentioning

confidence: 99%

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

et al. 2021

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“…However, MMP-9 deficiency in mouse models led to increased interleukin-6 levels in the bone marrow, which promoted pancreatic ductal adenocarcinoma (PDAC) invasion and metastasis. Furthermore, VEGF may also serve as an driver because it can lead to upregulation of other pro-angiogenic factors ( 24 ). Vascular endothelial growth factor and MMP-9 are shown to be a key target in the “angiogenic on-off.”…”

Section: Discussionmentioning

confidence: 99%

“…invasion and metastasis. Furthermore, VEGF may also serve as an driver because it can lead to upregulation of other pro-angiogenic factors (24). Vascular endothelial growth factor and MMP-9 are shown to be a key target in the "angiogenic on-off.…”

Section: Data Availability Statementmentioning

confidence: 99%

ORMDL3 Promotes Angiogenesis in Chronic Asthma Through the ERK1/2/VEGF/MMP-9 Pathway

et al. 2022

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AimAngiogenesis plays a vital role in airway remodeling in chronic asthma. ORMDL3 has been identified to be closely associated with the development of asthma remodeling. This study was to investigate the mechanism of ORMDL3 in angiogenesis of chronic asthma.MethodsBALB/c mice were divided into three groups, including an asthmatic group (group A), a budesonide-treated group (group B), and a normal control group (group C). Hematoxylin and eosin and Masson staining were used to evaluate the pathological changes. Angiogenesis in lung tissue was examined by CD31 staining. The changes of ORMDL3, ERK1/2, and angiogenesis-associated MMP-9 and Vascular endothelial growth factor (VEGF) expression were examined. Furthermore, ORMDL3, MMP-9, and VEGF mRNA and protein levels were examined after transfection in BEAS-2B cells with the ORMDL3-overexpressed lentiviral vector.ResultsCompared with the control group, asthmatic mice indicated more severe airway angiogenesis with increased ORMDL3, ERK1/2, MMP-9, and VEGF expression. Budesonide alleviated airway angiogenesis, and CD31 expression was positive with the levels of ORMDL3, MMP-9, and VEGF (P < 0.01). After successful transfection in BEAS-2B cells with the ORMDL3-overexpressing lentiviral vector, VEGF, and MMP-9 expression were activated in vitro (P < 0.01).ConclusionIn conclusion, our study provides novel evidence that ORMDL3 promotes angiogenesis through upregulating VEGF and MMP-9 in chronic asthma.

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“…EMT regulation by growth factors and others also showed that extrinsic factors, including IL-6, Tnf, TGF-b, Notch, Wnt, and receptor tyrosine kinase EGF, HGF, PDGF, FGF, etc., can further enhance cell invasion ability and facilitate cells to secrete matrix metalloproteinases (MMPs) to digest ECM [ 179 , 180 , 181 ]. Currently, approximately 23 MMP members have been identified [ 181 ].…”

Section: Defined Emt Molecules In Cancermentioning

confidence: 99%

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

Hsu

Chang

et al. 2021

Biomedicines

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Epithelial and mesenchymal transition mechanisms continue to occur during the cell cycle and throughout human development from the embryo stage to death. In embryo development, epithelial-mesenchymal transition (EMT) can be divided into three essential steps. First, endoderm, mesoderm, and neural crest cells form, then the cells are subdivided, and finally, cardiac valve formation occurs. After the embryonic period, the human body will be subjected to ongoing mechanical stress or injury. The formation of a wound requires EMT to recruit fibroblasts to generate granulation tissues, repair the wound and re-create an intact skin barrier. However, once cells transform into a malignant tumor, the tumor cells acquire the characteristic of immortality. Local cell growth with no growth inhibition creates a solid tumor. If the tumor cannot obtain enough nutrition in situ, the tumor cells will undergo EMT and invade the basal membrane of nearby blood vessels. The tumor cells are transported through the bloodstream to secondary sites and then begin to form colonies and undergo reverse EMT, the so-called “mesenchymal-epithelial transition (MET).” This dynamic change involves cell morphology, environmental conditions, and external stimuli. Therefore, in this manuscript, the similarities and differences between EMT and MET will be dissected from embryonic development to the stage of cancer metastasis.

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Role of Matrix Metalloproteinases in Angiogenesis and Its Implications in Asthma

Cited by 29 publications

References 100 publications

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

ORMDL3 Promotes Angiogenesis in Chronic Asthma Through the ERK1/2/VEGF/MMP-9 Pathway

Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis

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