2. Academic Validation
  3. mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage

mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage

  • BMC Mol Cell Biol. 2024 Apr 23;25(1):13. doi: 10.1186/s12860-024-00509-5.
Zeyong Huang 1,  Wenbin Teng # 2,  Liuxu Yao 3,  Kai Xie 4,  Suqin Hang 1,  Rui He 5,  Yuhong Li 6 7
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren College, 310015, Hangzhou, China.
  • 2 Department of Anesthesiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 310001, Hangzhou, China.
  • 3 Rehabilitation Medicine Center, Department of Anesthesiology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, 310014, Hangzhou, China.
  • 4 Department of Anesthesiology, Shaoxing People's Hospital, Zhejiang University, 312000, Shaoxing, China.
  • 5 Department of Anesthesiology, Shaoxing People's Hospital, Zhejiang University, 312000, Shaoxing, China. 15347172@qq.com.
  • 6 Department of Anesthesiology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren College, 310015, Hangzhou, China. yuh_li@zju.edu.cn.
  • 7 Department of Anesthesiology, Shulan (Hangzhou) Hospital, Shulan International Medical College, Shuren University, 848 Dongxin Road, Xiacheng District, 310004, Hangzhou, Zhejiang, China. yuh_li@zju.edu.cn.
  • # Contributed equally.
PMID: 38654163 DOI: 10.1186/s12860-024-00509-5
Abstract

Background: Sepsis-induced small-intestinal injury is associated with increased morbidity and mortality. Our previous study and other papers have shown that HIF-1α has a protective effect on intestinal mucosal injury in septic rats. The purpose of this study is to further verify the protective effect of HIF-1α on intestinal mucosa and its molecular mechanism in vitro experiments.

Methods: Caco-2 cells were selected and experiment was divided into 2 parts. Part I: HIF-1α activator and inhibitor were used to treat lipopolysacchrides (LPS)-stimulated Caco-2 cells respectively, to explore the effect of HIF-1α on LPS induced Caco-2 cell epithelial model; Part II: mTOR Activator or inhibitor combined with or without HIF-1α activator, inhibitor to treat LPS-stimulated Caco-2 cells respectively, and then the molecular mechanism of HIF-1α reducing LPS induced Caco-2 cell epithelial model damage was detected.

Results: The results showed that HIF-1α activator decreased the permeability and up regulated tight junction (TJ) expression, while HIF-1α Inhibitor had the opposite effect with the HIF-1α activator. mTOR activation increased, while mTOR inhibition decreased HIF-1α protein and expression of its downstream target molecules, which can be attenuated by HIF-1α activator or inhibitor.

Conclusion: This study once again confirmed that HIF-1α alleviates LPS-induced mucosal epithelial model damage through p70S6K signalling pathway. It is of great value to explore whether HIF-2α plays crucial roles in the regulation of mucosal epithelial model functions in the future.

Keywords

Caco-2 cells; Hypoxia-inducible factor-1α; In vitro; LPS induced intestinal epithelial model injury; mTOR/P70S6K signalling pathway.

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