House dust mite induces Sonic hedgehog signaling that mediates epithelial‑mesenchymal transition in human bronchial epithelial cells

Zou,Yimin; Song,Wenjuan; Zhou,Lingxiao; Mao,Yanxiong; Hong,Wei

doi:10.3892/mmr.2019.10707

House dust mite induces Sonic hedgehog signaling that mediates epithelial‑mesenchymal transition in human bronchial epithelial cells

Authors:
- Yimin Zou
- Wenjuan Song
- Lingxiao Zhou
- Yanxiong Mao
- Wei Hong
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Affiliations: Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Economics, School of Economics and Management, Zhejiang Sci‑Tech University, Hangzhou, Zhejiang 310018, P.R. China, Biological Laboratory Center, Guangzhou Institute of Biomedicine and Health Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510030, P.R. China
Published online on: September 26, 2019 https://doi.org/10.3892/mmr.2019.10707
Pages: 4674-4682
Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial‑mesenchymal transition (EMT) provides a valuable source of fibroblasts that produce extracellular matrix in airway walls. The Sonic hedgehog (SHH) signaling pathway plays an essential role in regulating tissue turnover and homeostasis. SHH is strikingly upregulated in the bronchial epithelia during asthma. Snail1 is a major target of SHH signaling, which regulates EMT and fibroblast motility. The present study was designed to ascertain whether the combination of house dust mite (HDM) and transforming growth factor β1 (TGF‑β1) could induce EMT via the SHH signaling pathway in human bronchial epithelial cells (HBECs). HBEC cultures were treated with HDM/TGF‑β1 for different periods of time. The involvement of SHH signaling and EMT biomarkers was evaluated by quantitative real‑time PCR, western blotting and immunofluorescence staining. Small‑interfering RNA (siRNA) for glioma‑associated antigen‑1 (Gli1) or cyclopamine was used to inhibit SHH signaling in HBECs. HBECs stimulated by HDM/TGF‑β1 exhibited morphological features of EMT. E‑cadherin (an epithelial marker) was decreased after a 72‑h exposure to HDM/TGF‑β1 compared to that in the control cells, and the expression of type I collagen and FSP1 (mesenchymal markers) was increased. HDM/TGF‑β1 activated the SHH signaling pathway in HBECs, which led to Gli1 nuclear translocation and the transcriptional activation of Snail1 expression. Moreover, gene silencing or the pharmacological inhibition of Gli1 ameliorated EMT. In summary, these findings suggest that HDM/TGF‑β1 may induce EMT in HBECs via an SHH signaling mechanism. Inhibition of SHH signaling may be a novel therapeutic method for preventing airway remodeling in asthma.

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