β-catenin as a regulator and therapeutic target for asthmatic airway remodeling

Kumawat, Kuldeep; Koopmans, Tim; Gosens, Reinoud

doi:10.1517/14728222.2014.934813

Cited by 53 publications

(53 citation statements)

References 86 publications

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“…Toward developing a mechanistic understanding of the effects of insulin on the lung, we show that ␤-catenin signaling is enhanced by insulin in vitro and in vivo. ␤-Catenin has been previously implicated in cell proliferation and EMT (22,30). Previous studies have also confirmed the role of ␤-catenin in ASM cell contraction (18).…”

Section: Discussionmentioning

confidence: 64%

Hyperinsulinemia adversely affects lung structure and function

Singh

Bodas

Bhatraju

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionmentioning

confidence: 64%

Hyperinsulinemia adversely affects lung structure and function

Singh

Bodas

Bhatraju

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Those decreased in expression are involved in the extracellular matrix, and the whole profile is important for cellular assembly (Fig 1, A ). Interestingly, hydrolase activity is known to be important for calcium signaling in ASM, 9 and the extracellular matrix is involved in asthmatic airway remodeling 10 . In the ASMCs from the patients with severe asthma, these profiles changed to an increase in genes necessary for arachidonic acid metabolism and a decrease in those required for multicellular organismal process, and the whole profile is involved in gene expression and organ morphology.…”

Section: Resultsmentioning

confidence: 99%

“…Of the mRNAs we examined, we found that the mRNA profile differentially regulated in ASMCs from patients with nonsevere asthma is important in ASMC calcium signaling, 9 airway remodeling, 10 the inflammatory response, 13 and glucocorticoid activity 15, 16. Interestingly, the mRNA profile in ASMCs from patients with severe asthma appears to be important in increased calcium influx in the smooth muscle, 11 atopy, 12 and possible immunomodulation in patients with acute exacerbations of airway disease, including asthma 14 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation ( PVT1 ) as a novel regulator of the asthmatic phenotype in human airway smooth muscle

Austin

Tsitsiou

Boardman

et al. 2017

Journal of Allergy and Clinical Immunology

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BackgroundThe mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma.MethodsPrimary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined.ResultsThe mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma.ConclusionslncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients.

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“…A previous study demonstrated that ~90% of cases of colon cancer were associated with excessive activation of this pathway (4). β-catenin is the key molecule of the Wnt/β-catenin signaling pathway (5). Thus, silencing the β-catenin gene may inhibit the development and invasion of colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of β-catenin by siRNA influences proliferation, apoptosis and invasion of the colon cancer cell line SW480

Zhou

et al. 2016

Oncology Letters

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Abstract. The aim of the present study was to explore the effect of knocking down the expression of β-catenin by small interference (si)RNA on the activity of the Wnt/β-catenin signaling pathway, and the proliferation, apoptosis and invasion abilities of the human colon cancer cell line SW480. For that purpose, double-stranded siRNA targeting β-catenin (β-catenin-siRNA) was synthesized and transfected into SW480 cells. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the messenger (m)RNA and protein levels of β-catenin in SW480 cells. To detect cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed, while cell apoptosis and caspase-3 activity were detected by flow cytometry and caspase-3 activity assay, respectively. Matrigel invasion assay was performed to detect the influence of siRNA-mediated gene silencing on the invasion and metastasis of SW480 cells in vitro. The results of RT-PCR and western blot analysis demonstrated that, compared with the blank control, negative control and liposome groups, β-catenin-siRNA transfected SW480 cells had significantly decreased mRNA and protein levels of β-catenin. In addition, following β-catenin-siRNA transfection, the proliferation of SW480 cells was significantly lower than that of the blank control, negative control and liposome groups, while the apoptosis rate increased in β-catenin-siRNA transfected cells, compared with the aforementioned groups. Invasion assay showed that, following β-catenin-siRNA transfection, the number of SW480 cells infiltrating through the Matrigel membrane was significantly lower than that of the blank control, negative control and liposome groups. Following β-catenin-siRNA transfection, the caspase-3 activity in SW480 cells was lower than that in the blank control, negative control and liposome groups. These results indicate that siRNA-mediated silencing of β-catenin could inhibit the proliferation and invasion of SW480 cells and induce apoptosis, thus providing novel potential strategies for the clinical treatment of colon cancer, and may serve as a novel target for cancer therapy.

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β-catenin as a regulator and therapeutic target for asthmatic airway remodeling

Cited by 53 publications

References 86 publications

Hyperinsulinemia adversely affects lung structure and function

Hyperinsulinemia adversely affects lung structure and function

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation ( PVT1 ) as a novel regulator of the asthmatic phenotype in human airway smooth muscle

Knockdown of β-catenin by siRNA influences proliferation, apoptosis and invasion of the colon cancer cell line SW480

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