Abstract | NEW FINDINGS: ABSTRACT: Epithelial-to-mesenchymal transition (EMT) of airway remodelling happens in children with asthma. A reduction in the epithelial marker E-cadherin is reported to be one of the initiating factors of EMT. Our previous study showed that chromatin remodelling factor brahma-related gene-1 (BRG1) could regulate the expression of E-cadherin indirectly. However, the transcription factor involved in the recruitment of BRG1 in asthma is unknown. Here, we studied the function of Brg1 in an ovalbumin-induced asthma model [lung-specific conditional Brg1 knockdown (Brg1-/- ) mice] and human bronchial epithelial 16HBE cells stably expressing BRG1 short hairpin RNA. Our results showed that Brg1 was involved in EMT in asthmatic mice by detecting the expression of EMT markers. We also identified that BRG1 participated in the transforming growth factor-β-induced EMT of 16HBE cells. We observed that zinc finger E-box binding homeobox 1 (ZEB1) and BRG1 co-localized in the EMT of TGF-β-induced 16HBE cells. Further results revealed that ZEB1 recruited BRG1 and bound to the promoter region (+3563/3715) to regulate E-cadherin expression. Thus, ZEB1 might be the key transcription factor to recruit BRG1 in airway remodelling EMT of asthma and might be a new therapeutic target.
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Authors | Ting Wang, Bingming Peng, Tingting Luo, Daiyin Tian, Zhihua Zhao, Zhou Fu, Qubei Li |
Journal | Experimental physiology
(Exp Physiol)
Vol. 107
Issue 5
Pg. 515-526
(05 2022)
ISSN: 1469-445X [Electronic] England |
PMID | 35138000
(Publication Type: Journal Article)
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Copyright | © 2022 The Authors. Experimental Physiology © 2022 The Physiological Society. |
Chemical References |
- Cadherins
- Nuclear Proteins
- Transcription Factors
- ZEB1 protein, mouse
- Zinc Finger E-box-Binding Homeobox 1
- Smarca4 protein, mouse
- DNA Helicases
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Topics |
- Airway Remodeling
- Animals
- Asthma
(metabolism)
- Cadherins
(metabolism)
- DNA Helicases
- Epithelial-Mesenchymal Transition
(physiology)
- Mice
- Nuclear Proteins
- Transcription Factors
- Zinc Finger E-box-Binding Homeobox 1
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