DEK‐targeting aptamer DTA‐64 attenuates bronchial EMT‐mediated airway remodelling by suppressing TGF‐β1/Smad, MAPK and PI3K signalling pathway in asthma

Song, Yang; Wang, Zhiguang; Jiang, Jingzhi; Piao, Yihua; Li, Li; Xu, Chang; Piao, Hulin; Yan, Guanghai

doi:10.1111/jcmm.15942

Cited by 44 publications

(25 citation statements)

References 34 publications

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“…In the process of airway remodeling, there is a phenotypic transformation of airway epithelial cells to mesenchymal morphology, including E-cadherin reduction and an increase in N-calcium expression, which can lead to a decrease in glucocorticoid sensitivity and severely affect the prognosis. 50,51 Studies have shown that TGF-β1 can regulate the miR-203a-3p/SIX1 signaling pathway to regulate the Smad3 pathway and promote the occurrence of epithelial-mesenchymal transition in asthma. 52 In vivo and in vitro experiments have found that icariin can significantly inhibit the phosphorylation of cytokines such as Erk, JNK, and p38; inhibit the activation of Smad and MAPK signaling pathways; and reduce the EMT process induced by TGF-β1 to improve airway remodeling.…”

Section: Icariin Could Inhibit Airway Epithelial Cell-to-mesenchymal Transition (Emt)mentioning

confidence: 99%

Research progress of icariin, an extract of traditional Chinese medicine, in the treatment of asthma

Yuan

Tong

Dong

et al. 2022

aei

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Bronchial asthma is a common chronic airway disease, and long-term management of asthma is the focus and difficulty of clinical treatment. Glucocorticoids are often used as the first choice for the treatment of asthma. However, the occurrence of hormone dependence, hormone resistance, local and systemic adverse reactions caused by hormone application also brings problems for the treatment of asthma. Finding safe and effective new therapeutic drugs is an important research direction at present. Icariin is the effective ingredient of traditional Chinese medicine Epimedium. It has various biological activities such as anti-inflammatory, anti-oxidative stress, and immune regulation. It has high safety and has a wide range of clinical applications. Icariin has the characteristics of multi-target intervention in the treatment of asthma. This article reviews recent studies in order to provide new research directions for further therapeutic drug development.

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Section: Icariin Could Inhibit Airway Epithelial Cell-to-mesenchymal Transition (Emt)mentioning

confidence: 99%

Research progress of icariin, an extract of traditional Chinese medicine, in the treatment of asthma

Yuan

Tong

Dong

et al. 2022

aei

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“…TGF- β 1-mediated signaling pathways, such as Smad2/3, p38, ERK1/2, and JNK MAPK, play important roles in epithelium injury and the EMT process in asthma [ 24 , 25 ]. Therefore, we first detected the related protein expression of the Smad2/3 and MAPKs pathway by Western blot to explore whether the regulatory mechanism of osthole treatment on cell apoptosis and EMT of 16HBE cells with TGF- β 1 induction was associated with activation of the Smad2/3 and MAPKs pathway mediated by TGF- β 1.…”

Section: Resultsmentioning

confidence: 99%

The Role of Osthole on TGF-β-Induced Lung Epithelium Apoptosis Injury and Epithelial-Mesenchymal Transition-Mediated Airway Remodeling in Pediatric Asthma

Tang

Liu²,

Zhang

2022

Journal of Healthcare Engineering

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Osthole, a coumarin compound derived from Fructus Cnidii, exerts anti-inflammatory effects in an asthma model. But the effect of osthole on epithelial injury and epithelial-mesenchymal transition (EMT) in asthma remains unclear. 16HBE cells were incubated with TGF-β1 with or without osthole in vitro. Ovalbumin (OVA)-induced asthmatic mouse model was established in vivo. Cell counting kit-8 was carried out to evaluate the viability of 16HBE cells. The impact of osthole on TGF-β1-evoked cell apoptosis and EMT process was measured by flow cytometry based on Annexin V-FITC/PI staining, transwell assay, immunofluorescence, and Western blot. The regulatory role of osthole in TGF-β1/Smad and p38, ERK1/2, and JNK MAPK signaling was detected via Western blot. Osthole treatment significantly suppressed TGF-β1-induced 16HBE cell apoptosis, verified by a reduced percentage of apoptotic cells, decreased expression of proapoptotic proteins (cleaved-caspase3 and Bax), and enhanced antiapoptotic factor (Bcl-2) expression. In addition, the promotive impact of TGF-β1 on the migration of 16HBE cells was reversed by osthole, accompanied by elevated E-cadherin expression and reduced Snail and N-cadherin expression. The activation of the Smad2/3 and MAPKs pathway evoked by TGF-β1 was inhibited by osthole in 16HBE cells. We also found that osthole mitigated airway epithelium injury and subepithelial fibrosis in OVA-challenged asthmatic mice in vivo. Osthole could mitigate TGF-β1-induced epithelial cell injury and EMT process by suppressing the activation of MAPK and Smad2/3 pathways separately. Our present study showed a new insight into understanding the underlying mechanism of osthole injury on epithelium injury and subepithelial fibrosis in airway remodeling. Asthma, epithelial injury, epithelial-mesenchymal transition, and airway remodeling are the effects of osthole on airway remodeling.

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“…Several upstream signaling pathways such as MAPK, PI3K/AKT, and TGF-β can regulate EMT [21,22] . The MAPK JNK/p38 signaling pathway plays a vital role in tumor invasion and metastasis [23] , and induces EMT, which has an impact on tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

Silencing of CMTM6 Inhibits the Proliferation and Migration of SiHa Cervical Cancer Cells by Inhibiting MAPK Signaling

Huang

Liu

et al. 2021

Preprint

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Background: CKLF like MARVEL transmembrane domain containing 6 (CMTM6) is an important programmed cell death 1 ligand 1 (PD-L1) regulator. CMTM6 was identified as an immune checkpoint inhibitor，that regulates tumor T cell activity in vivo and in vitro. The function of CMTM6 in cervical cancer, however, remains unclear. In addition, whether CMTM6 participates in ovarian cancer epithelial-mesenchymal transition (EMT) is unknown.Methods: Immunohistochemistry was used to detect CMTM6 expression in cervical cancer tissues and non-cancerous adjacent tissues. CMTM6 was knocked down and overexpressed, respectively, in the human SiHa cell line. Transwell and wound healing assays were used to assess cell migration and cell invasion. Western blotting was used to detect phosphorylated (p)-C-Jun N-terminal kinase (JNK)1/2, total (t)-JNK1/2, p-p38, t-p38, and EMT-related protein levels in Siha cells. In vivo lung transplantation tumor models were used to determine if CMTM6 upregulation in ovarian cancer cells could promote metastasis.Results: CMTM6 showed higher expression in human ovarian cancer tissues than in adjacent non-cancerous tissues. In vitro assays showed that CMTM6 promoted ovarian cancer cell invasion, migration, proliferation, and EMT via MAPK JNK/p38 signaling pathway activation. Stimulating CMTM6-overexpressing cells with MAPK JNK/p38 signaling antagonists reduced SiHa cell metastasis, invasion, proliferation and EMT. In a mouse model of lung metastasis, CMTM6 increased the metastasis of ovarian cancer. Conclusion: CMTM6 activates MAPK JNK/p38 signaling to enhance the EMT and metastasis of ovarian cancer cells. These results suggest CMTM6 as a molecular target for the prevention and treatment of ovarian cancer metastasis.

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DEK‐targeting aptamer DTA‐64 attenuates bronchial EMT‐mediated airway remodelling by suppressing TGF‐β1/Smad, MAPK and PI3K signalling pathway in asthma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 44 publications

References 34 publications

Research progress of icariin, an extract of traditional Chinese medicine, in the treatment of asthma

Research progress of icariin, an extract of traditional Chinese medicine, in the treatment of asthma

The Role of Osthole on TGF-β-Induced Lung Epithelium Apoptosis Injury and Epithelial-Mesenchymal Transition-Mediated Airway Remodeling in Pediatric Asthma

Silencing of CMTM6 Inhibits the Proliferation and Migration of SiHa Cervical Cancer Cells by Inhibiting MAPK Signaling

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