Hypoxia-inducible factor-1α mediating the expression of monocarboxylate transporter-1 and participating in the protective effect of short-chain fatty acids on intestinal hypoxia

doi:10.3877/cma.j.issn.1674-0793.2023.01.004

Abstract

Abstract:

Objective

To investigate the regulation of hypoxia-inducible factor-1α (HIF-1α)on monocarboxylate transporter-1 (MCT-1) expression in intestinal epithelial cells under hypoxia, and the protective effects of short-chain fatty acids (SCFAs) on intestinal barrier under hypoxia.

Methods

Normal ileum and ischemic ileum were resected and stained by immunohistochemistry targeting MCT-1. Normal C57 mice, intestinal epithelial-specific HIF-1α^ΔIEC mice and HIF-1α^flox/flox controlled mice were randomly divided into Sham group, ischemia reperfusion (I/R) group, I/R plus butyrate group. The distal ileum tissues were collected for immunohistochemical staining and the intestinal fluid in the intestinal lumen was detected for SCFAs. Intestinal epithelial cell line Caco-2 was cultured and hypoxia model was established. The cells were divided into control group, hypoxia group, hypoxia+siHIF-1α group, hypoxia+butyrate group and siMCT-1+hypoxia+butyrate group. Expression of MCT-1, HIF-1α and tight junction protein were detected by Western blotting. Changes in intestinal epithelial barrier function were assessed by transepithelial electrical resistance (TER).

Results

Compared with Sham group, intestinal SCFAs in I/R group did not change significantly. Both ischemia and hypoxia could induce high expression of MCT-1 in intestinal epithelial cells. HIF-1α^ΔIEC mice had lower intestinal MCT-1 expression than the control group and were more sensitive to I/R injury. Butyrate mediated intestinal barrier protection and up-regulated tight junction proteins Claudin1 and Occludin when HIF-1α and MCT-1 were normally expressed.

Conclusion

HIF-1α mediates the expression of MCT-1 in intestinal epithelial cells during hypoxia and participates in the protection of intestinal barrier by SCFAs.

Key words: Hypoxia-inducible factor-1α, Ischemia reperfusion injury, Short-chain fatty acids, Monocarboxylate transporter-1, Intestinal barrier

Xiuyang Zhang, Longfei Zhang, Shiyuan Chen, Yong Gao. Hypoxia-inducible factor-1α mediating the expression of monocarboxylate transporter-1 and participating in the protective effect of short-chain fatty acids on intestinal hypoxia[J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(01): 18-23.

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References 22

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