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Metabolomic profiling identifies a novel mechanism for heat stroke‑related acute kidney injury
Metabolomic profiling identifies a novel mechanism for heat stroke‑related acute kidney injury
- Source :
- Molecular Medicine Reports
- Publication Year :
- 2021
- Publisher :
- Spandidos Publications, 2021.
-
Abstract
- Heat stroke can induce a systemic inflammatory response, which may lead to multi‑organ dysfunction including acute kidney injury (AKI) and electrolyte disturbances. To investigate the pathogenesis of heat stroke (HS)‑related AKI, a mouse model of HS was induced by increasing the animal's core temperature to 41˚C. Blood samples obtained from the tail vein were used to measure plasma glucose and creatinine levels. Micro‑positron emission tomography‑computed tomography (micro‑PET/CT), Hamp;E staining and transmission electron microscopy were conducted to examine metabolic and morphological changes in the mouse kidneys. Immunohistochemistry (IHC) and western blot analyses were performed to investigate the expression of apoptosis‑inducing factor mitochondria‑associated 2 (Aifm2), high‑mobility group box 1 (HMGB1) and receptor for advanced glycosylation end products (RAGE). Liquid chromatography‑mass spectrometry analysis was conducted to find differential metabolites and signaling pathways. The HS mouse model was built successfully, with significantly increased creatinine levels detected in the serum of HS mice compared with controls, whereas micro‑PET/CT revealed active metabolism in the whole body of HS mice. Hamp;E and TUNEL staining revealed that the kidneys of HS mice exhibited signs of hemorrhage and apoptosis. IHC and western blotting demonstrated significant upregulation of Aifm2, HMGB1 and RAGE in response to HS. Finally, 136 differential metabolites were screened out, and enrichment of the 'biosynthesis of unsaturated fatty acids' pathway was detected. HS‑associated AKI is the renal manifestation of systemic inflammatory response syndrome, and may be triggered by the HMGB1/RAGE pathway. Metabolomics indicated increased adrenic acid, docosahexaenoic acid and eicosapentaenoic acid may serve as metabolic biomarkers for AKI in HS. The findings suggested that a correlation between the HMGB1/RAGE pathway and biosynthesis of unsaturated fatty acids may contribute to the progression of HS‑related AKI.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
Heat Stroke
Receptor for Advanced Glycation End Products
Apoptosis
Kidney
HMGB1
Biochemistry
RAGE (receptor)
Pathogenesis
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Positron Emission Tomography Computed Tomography
Internal medicine
Genetics
Animals
Humans
Medicine
HMGB1 Protein
Molecular Biology
Creatinine
biology
business.industry
Acute kidney injury
Articles
Acute Kidney Injury
medicine.disease
metabolomics
Eicosapentaenoic acid
RAGE
Blot
Disease Models, Animal
030104 developmental biology
Endocrinology
Oncology
chemistry
Docosahexaenoic acid
030220 oncology & carcinogenesis
biology.protein
Molecular Medicine
Apoptosis Regulatory Proteins
Oxidoreductases
business
unsaturated fatty acids
Signal Transduction
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....577a216269dec61e55d66a0b3a010380
- Full Text :
- https://doi.org/10.3892/mmr.2021.11880