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DEK-targeting aptamer DTA-64 attenuates bronchial EMT-mediated airway remodelling by suppressing TGF-ß1/Smad, MAPK and PI3K signalling pathway in asthma.
Song, Yilan; Wang, Zhiguang; Jiang, Jingzhi; Piao, Yihua; Li, Li; Xu, Chang; Piao, Hongmei; Li, Liangchang; Yan, Guanghai.
Afiliação
  • Song Y; Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, China.
  • Wang Z; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, China.
  • Jiang J; Postdoctoral Programme, Research Center, Affiliated Hospital of Yanbian University, Yanji, China.
  • Piao Y; Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, China.
  • Li L; Department of Respiratory Medicine, Affiliated Hospital of Yanbian University, Yanji, China.
  • Xu C; Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, China.
  • Piao H; Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, China.
  • Li L; Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, China.
  • Yan G; Department of Intensive Care Unit, Affiliated Hospital of Yanbian University, Yanji, China.
J Cell Mol Med ; 24(23): 13739-13750, 2020 12.
Article em En | MEDLINE | ID: mdl-33124760
This study is to investigate the inhibitory effects and mechanisms of DEK-targeting aptamer (DTA-64) on epithelial mesenchymaltransition (EMT)-mediated airway remodelling in mice and human bronchial epithelial cell line BEAS-2B. In the ovalbumin (OVA)-induced asthmatic mice, DTA-64 significantly reduced the infiltration of eosinophils and neutrophils in lung tissue, attenuated the airway resistance and the proliferation of goblet cells. In addition, DTA-64 reduced collagen deposition, transforming growth factor 1 (TGF-ß1) level in BALF and IgE levels in serum, balanced Th1/Th2/Th17 ratio, and decreased mesenchymal proteins (vimentin and α-SMA), as well as weekend matrix metalloproteinases (MMP-2 and MMP-9) and NF-κB p65 activity. In the in vitro experiments, we used TGF-ß1 to induce EMT in the human epithelial cell line BEAS-2B. DEK overexpression (ovDEK) or silencing (shDEK) up-regulated or down-regulated TGF-ß1 expression, respectively, on the contrary, TGF-ß1 exposure had no effect on DEK expression. Furthermore, ovDEK and TGF-ß1 synergistically promoted EMT, whereas shDEK significantly reduced mesenchymal markers and increased epithelial markers, thus inhibiting EMT. Additionally, shDEK inhibited key proteins in TGF-ß1-mediated signalling pathways, including Smad2/3, Smad4, p38 MAPK, ERK1/2, JNK and PI3K/AKT/mTOR. In conclusion, the effects of DTA-64 against EMT of asthmatic mice and BEAS-2B might partially be achieved through suppressing TGF-ß1/Smad, MAPK and PI3K signalling pathways. DTA-64 may be a new therapeutic option for the management of airway remodelling in asthma patients.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Asma / Proteínas Cromossômicas não Histona / Transdução de Sinais / Proteínas Oncogênicas / Aptâmeros de Nucleotídeos / Transição Epitelial-Mesenquimal / Proteínas de Ligação a Poli-ADP-Ribose Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Asma / Proteínas Cromossômicas não Histona / Transdução de Sinais / Proteínas Oncogênicas / Aptâmeros de Nucleotídeos / Transição Epitelial-Mesenquimal / Proteínas de Ligação a Poli-ADP-Ribose Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article