Hypoxic preconditioning accelerates the healing of ischemic intestinal injury by activating HIF-1α/PPARα pathway-mediated fatty acid oxidation

Hypoxic preconditioning accelerates the healing of ischemic intestinal injury by activating HIF-1α/PPARα pathway-mediated fatty acid oxidation

Hypoxic preconditioning (HPC) has been shown to improve organ tolerance to subsequent severe hypoxia or ischemia. However, its impact on intestinal ischemic injury has not been well studied. In this study, we evaluated the effects of HPC on intestinal ischemia in rats. Intestinal rehabilitation, lev...

Full description

Saved in:
Bibliographic Details
Published in:Cell death discovery Vol. 10; no. 1; p. 164
Main Authors: Li, Linxia, Liu, Yanqi, Zhi, Na, Ji, Yaoxuan, Xu, Jialing, Mao, Guoyun, Wang, Yazhou, Ma, Jin, Wang, Yunying
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 04-04-2024
Springer Nature B.V
Nature Publishing Group
Subjects:
631/532
692/699/1503
Apoptosis
Biochemistry
Biomedical and Life Sciences
Carnitine palmitoyltransferase
Cell activation
Cell Biology
Cell Cycle Analysis
Fatty acids
Hypoxia
Hypoxia-inducible factor 1
Hypoxia-inducible factor 1a
Ischemia
Life Sciences
mRNA
Oxidation
Palmitoyltransferase
Peroxisome proliferator-activated receptors
Small intestine
Stem Cells
Wound healing
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hypoxic preconditioning (HPC) has been shown to improve organ tolerance to subsequent severe hypoxia or ischemia. However, its impact on intestinal ischemic injury has not been well studied. In this study, we evaluated the effects of HPC on intestinal ischemia in rats. Intestinal rehabilitation, levels of fatty acid oxidation (FAO) by-products, intestinal stem cells (ISCs), levels of hypoxia-inducible factor 1 subunit α (HIF-1α) and its downstream genes such as peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyltransferase 1a (CPT1A) were assessed at distinct time intervals following intestinal ischemia with or without the interference of HIF-1α. Our data showed that HPC facilitates the restoration of the intestinal structure and enhances the FAO, by boosting intestinal stem cells. Additionally, HIF-1α, PPARα, and CPT1A mRNA and their protein levels were generally up-regulated in the small intestine of HPC rats as compared to the control group. Our vitro experiment also shows low-oxygen induces highly levels of HIF-1α and its downstream genes, with a concurrent increase in FAO products in IEC-6 cells. Furthermore, the above phenomenon could be reversed by silencing HIF-1α. In conclusion, we hypothesize that HPC can stimulate the activation of intestinal stem cells via HIF-1α/PPARα pathway-mediated FAO, thereby accelerating the healing process post ischemic intestinal injury.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-024-01937-0