Expression of DACT1 in children with asthma and its regulation mechanism

  • Authors:
    • Cunxue Zhang
    • Peili Yang
    • Yan Chen
    • Jing Liu
    • Xiutai Yuan
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  • Published online on: January 5, 2018     https://doi.org/10.3892/etm.2018.5706
  • Pages: 2674-2680
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Abstract

The aim of the present study was to detect DACT1 expression levels in the lungs of children with asthma, and to investigate its role and molecular mechanisms in regulating the expression of inflammatory factors in RAW264.7 cells. DACT1, DACT2 and DACT3 expression was analyzed in biopsy specimens from 10 cases of newly diagnosed children with asthma and 10 healthy controls by reverse transcription‑quantitative polymerase chain reaction, and their expression was confirmed in RAW264.7 cells. DACT1 expression was silenced by small interfering RNA or enhanced by transfection of pcDNA‑3.1‑DACT1 in RAW264.7 cells, and expression of β‑catenin and inflammatory factors, interleukin (IL) 5, IL6 and IL13, was analyzed. Nuclear translocation of β‑catenin was detected by western blot analysis, and the effect of DACT1 on β‑catenin was investigated with rescue experiments. Regulation of the Wnt signaling pathway by DACT1 and β‑catenin was analyzed in RAW264.7 cells after recombinant Wnt5A stimulation. DACT1, DACT2 and DACT3 were significantly upregulated in specimens from children with asthma compared with controls (P<0.05) and the expression of DACT1 was significantly more increased compared with DACT2 and DACT3 (P<0.05). Inhibition of DACT1 expression significantly suppressed IL5, IL6 and IL13 mRNA expression levels compared with the control (P<0.05), while upregulated DACT1 expression significantly increased IL5, IL6 and IL13 mRNA expression (P<0.05). DACT1 inhibited the expression and nuclear translocation of β‑catenin, while overexpression of β‑catenin significantly inhibited the biological function of DACT1 (P<0.05). Overexpression of β‑catenin also significantly suppressed the upregulation of IL5, IL6 and IL13 mRNA induced by pcDNA3.1‑DACT1 transfection (P<0.05). Following the addition of Wnt5A, overexpression of DACT1 inhibited the expression and nuclear translocation of β‑catenin, and upregulated IL5, IL6 and IL13 mRNA expression. In conclusion, DACT1 was indicated to be upregulated in lung tissues from children with asthma, which could induce higher pro‑inflammatory factor expression. DACT1 may act via inhibiting the expression and nuclear translocation of β‑catenin, a factor in the Wnt signaling pathway. The present results suggested that DACT1 may be a potential target for the treatment of asthma.
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March-2018
Volume 15 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang C, Yang P, Chen Y, Liu J and Yuan X: Expression of DACT1 in children with asthma and its regulation mechanism. Exp Ther Med 15: 2674-2680, 2018
APA
Zhang, C., Yang, P., Chen, Y., Liu, J., & Yuan, X. (2018). Expression of DACT1 in children with asthma and its regulation mechanism. Experimental and Therapeutic Medicine, 15, 2674-2680. https://doi.org/10.3892/etm.2018.5706
MLA
Zhang, C., Yang, P., Chen, Y., Liu, J., Yuan, X."Expression of DACT1 in children with asthma and its regulation mechanism". Experimental and Therapeutic Medicine 15.3 (2018): 2674-2680.
Chicago
Zhang, C., Yang, P., Chen, Y., Liu, J., Yuan, X."Expression of DACT1 in children with asthma and its regulation mechanism". Experimental and Therapeutic Medicine 15, no. 3 (2018): 2674-2680. https://doi.org/10.3892/etm.2018.5706