Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p‐STAT3 in Helicobacter pylori‐associated gastritis

BHLHE40, a member of the basic helix‐loop‐helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)‐associated gastritis is unknown. We observed that gastric BHLHE40 was s...

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Bibliographic Details
Published in:The FASEB journal 2020-01, Vol.34 (1), p.1169-1181
Main Authors: Teng, Yong‐Sheng, Zhao, Yong‐Liang, Li, Mao‐Shi, Liu, Yu‐Gang, Cheng, Ping, Lv, Yi‐Pin, Mao, Fang‐Yuan, Chen, Weisan, Yang, Shi‐Ming, Hao, Chuan‐Jie, Peng, Liu‐Sheng, Zhang, Jin‐Yu, Zhang, Wei‐Jun, Zou, Quan‐Ming, Zhuang, Yuan
Format: Article
Language:English
Subjects:
BHLHE40
cagA
CXCL12
Helicobacter pylori
p‐STAT3
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Summary:BHLHE40, a member of the basic helix‐loop‐helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)‐associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pylori‐infected GECs express BHLHE40 via cagA‐ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein‐activated p‐STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4+ T cell infiltration in the gastric mucosa. Our results identify the cagA‐BHLHE40‐CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201900464RR