Lung Remodeling in a Mouse Model of Asthma Involves a Balance between TGF-β1 and BMP-7

Stumm, Camila L.; Halcsik, Erik; Landgraf, Richardt Gama; Câmara, Niels Olsen Saraiva; Sogayar, Mari Cleide; Jancar, Sônia

doi:10.1371/journal.pone.0095959

Cited by 43 publications

(42 citation statements)

References 27 publications

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“…FOXC1, which is a novel hypoxiainduced transcription factor, is upregulated in hypoxic areas of lung cancer tissues and plays a key role in the tumor microenvironment and promotes lung cancer progression [17]. TGF-β1 is a key mediator of fibrosis and induces the differentiation of fibroblasts into myofibroblasts, which are the effector cells in asthma whose expression is increased in asthma [46]. Compared with the blank group, the positive expression rates of FOXC1 and TGF-β1 in lung tissues were decreased in the miR-200a mimic groups.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

Liu¹,

Miao²,

Gào³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The etiology of asthma, which is a complicated disorder with various symptoms, including wheezing, coughing, and airflow obstruction, remains poorly understood. In addition, the effects of microRNAs (miRs) have not been explored. This study explored the effect of microRNA-200a (miR-200a) on airway smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, we speculated that miR-200a achieves its effect by targeting FOXC1 via the PI3K/AKT signaling pathway based on differentially expressed gene screening, target miR predictions and a bioinformatics analysis. Methods: Eighty mice were assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was transfected with a series of inhibitors, activators, and siRNAs to test the established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to leukocytes were detected. An ELISA was adopted to measure the levels of interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, and immunoglobulin E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1, TGF-β1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed to detect cell proliferation and flow cytometry to detect apoptosis and cell cycle entry. Results: The bioinformatics analysis indicated that miR-200a mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse models of asthma were established. An elevated expression of miR-200a, a decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1 and TGF-β1, a decreased expression of p-AKT, suppressed cell proliferation, accelerated apoptosis, and an increased number of cells at the G0/G1 phase were observed following the upregulation of miR-200a and downregulation of FOXC1. Conclusion: The overexpression of miR-200a may downregulate FOXC1, thereby inhibiting the activation of the PI3K/AKT signaling pathway and ultimately suppressing ASMC proliferation and airway remodeling in asthmatic mice. This evidence supports the potential that miR-200a represents a new approach to treating asthma.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

Liu¹,

Miao²,

Gào³

et al. 2018

Cell Physiol Biochem

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“…The increased level of TGF␤1 is observed in chronic allergic asthma induced by house dust mites (48). Asthma, induced by ovalbumin, involves the increased expression of TGF␤1 (49). TGaseII regulates the expression of TGF␤1 (50).…”

Section: Discussionmentioning

confidence: 99%

Transglutaminase II/MicroRNA-218/-181a Loop Regulates Positive Feedback Relationship between Allergic Inflammation and Tumor Metastasis

Eom

Kim

et al. 2014

Journal of Biological Chemistry

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Background:The mechanism of transglutaminase II-mediated allergic inflammation-promoted tumor metastasis remains unknown at the molecular level. Results: The transglutaminase II/miR-218/-181a loop regulates allergic inflammation-promoted tumor metastasis. Conclusion: Transglutaminase II mediates a positive feedback between allergic inflammation and tumor metastasis. Significance: Transglutaminase II can be a target for the development of allergy and cancer therapeutics.

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“…The mice were then subjected to specific BMP-7 therapy, which was found to be effective at inhibiting collagen type I induced by TGF-b1 [49]. The mouse studies offer promise for trials on the use of BMP proteins as markers of severe asthma associated with remodelling in humans.…”

Section: The Bmp Protein and Bmpr Receptor: Expression Function And mentioning

confidence: 99%

Selected Bone Morphogenetic Proteins—The Possibility of Their Use in the Diagnostics and Therapy of Severe Asthma

Koćwin

Jonakowski

Przemęcka

et al. 2017

Advances in Respiratory Medicine

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Asthma is a chronic heterogeneous illness of the lower airway with an inflammatory basis, developing from hyperresponsiveness and bronchial obstruction. One of the more unfavourable processes occurring in the airway are the long-term changes of the respiratory tract known as remodelling, resulting in complete irreversible obstruction. Bone morphogenetic protein (BMP) is a member of the Transforming Growth Factor beta (TGF-b) superfamily, which regulates processes in embryonic and post-embryonic development. The role played by BMP is regulation of degradation and remodelling of the extracellular matrix, which is one of the elements involved in the reconstruction of the structure of the bronchi in severe asthma. This paper presents the antagonistic properties of BMP against TGF-b, anti-inflammatory and counteracting fibrosis in the respiratory tract. The current state of knowledge indicates that this group of cytokines are potential new markers of remodelling in severe asthma, and further studies on their therapeutic value are necessary.

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Lung Remodeling in a Mouse Model of Asthma Involves a Balance between TGF-β1 and BMP-7

Cited by 43 publications

References 27 publications

MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice

Transglutaminase II/MicroRNA-218/-181a Loop Regulates Positive Feedback Relationship between Allergic Inflammation and Tumor Metastasis

Selected Bone Morphogenetic Proteins—The Possibility of Their Use in the Diagnostics and Therapy of Severe Asthma

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