Abstract
Background
Portal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis
and a potential cause of gastrointestinal bleeding. Mucosal apoptosis is an essential
pathological feature of PHG. However, whether HIF-1α and p53 are involved in mucosal
apoptosis and whether HIF-1α induces PHG by mediating p53 remains unclear.
Methods
Gastric mucosal injury and apoptosis were examined in PHG patients and animal models.
The mechanisms of HIF-1α- and p53-mediated apoptosis were analyzed. The GES-1 cell
line was used to elucidate the underlying mechanisms using siRNA knockdown of HIF-1α
and p53 in a hypoxic environment in vitro.
Results
Epithelial apoptosis, HIF-1α, and p53 were markedly induced in the gastric mucosa
of PHG. Apoptosis was attenuated in mice with HIF-1α- and p53-specific inhibitors.
Apoptotic signaling factors were markedly induced in the gastric mucosa of PHG. Inhibition
of p53 demonstrably attenuated the mucosal apoptosis; however, it did not affect HIF-1α
expression. Conversely, targeted deletion of HIF-1α significantly inhibited p53 expression
and attenuated the injury and p53-mediated apoptosis. Bax and Bcl-2 expression can
be upregulated and downregulated by p53, respectively, to increasecleaved caspase-3
expression, which can be regulated by HIF-1α.
Conclusions
These results indicate that HIF-1α regulates the p53-induced mucosal epithelial apoptotic
signaling pathway and that HIF-1α and p53 are potential therapeutic targets for PHG.
Keywords
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Article info
Publication history
Published online: June 29, 2022
Accepted:
June 13,
2022
Received:
May 11,
2022
Identification
Copyright
© 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
