期刊
JOURNAL OF PATHOLOGY
卷 253, 期 4, 页码 384-395出版社
WILEY
DOI: 10.1002/path.5602
关键词
ethanol; NOTCH; PAX9; RBPJ; NICD1; esophagus; esophageal squamous cell carcinoma
资金
- Young Scientist Program from Beijing Stomatological Hospital, Capital Medical University [YSP202006]
- Beijing Stomatological Hospital, Capital Medical University
- National Institutes of Health [U54 AA019765, R21 AA028047, U54 CA156735, U54 MD012392]
Alcohol exposure inhibits NOTCH signaling, leading to suppression of PAX9 expression in esophageal squamous epithelial cells. This study reveals a novel mechanism of alcohol-induced esophageal injury.
Alcohol drinking has been established as a major risk factor for esophageal diseases. Our previous study showed that ethanol exposure inhibited PAX9 expression in human esophageal squamous epithelial cells in vitro and in vivo. In this study, we aimed to investigate the molecular pathways through which alcohol drinking suppresses PAX9 in esophageal squamous epithelial cells. We first demonstrated the inhibition of NOTCH by ethanol exposure in vitro. NOTCH regulated PAX9 expression in KYSE510 and KYSE410 cells in vitro and in vivo. RBPJ and NOTCH intracellular domain (NIC) D1 ChIP-PCR confirmed Pax9 as a direct downstream target of NOTCH signaling in mouse esophagus. NOTCH inhibition by alcohol drinking was further validated in mouse esophagus and human tissue samples. In conclusion, ethanol exposure inhibited NOTCH signaling and thus suppressed PAX9 expression in esophageal squamous epithelial cells in vitro and in vivo. Our data support a novel mechanism of alcohol-induced esophageal injury through the inhibition of NOTCH-PAX9 signaling. (c) 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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