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Ten-eleven translocation methyl-cytosine dioxygenase 2 deficiency exacerbates renal ischemia-reperfusion injury
- Source :
- Clinical Epigenetics
- Publication Year :
- 2020
-
Abstract
- Background Ten-eleven translocation (Tet) methyl-cytosine dioxygenases (including Tet1/2/3)-mediated 5mC oxidation and DNA demethylation play important roles in embryonic development and adult tissue homeostasis. The expression of Tet2 and Tet3 genes are relatively abundant in the adult murine kidneys while Tet1 gene is expressed at a low level. Although Tet3 has been shown to suppress kidney fibrosis, the role of Tet2 in kidney physiology as well as renal ischemia-reperfusion (IR) injury is still largely unknown. Results Tet2−/− mice displayed normal kidney morphology and renal function as WT mice while the expression of genes associated with tight junction and adherens junction was impaired. At 24 h post-renal IR, Tet2−/− mice showed higher SCr and BUN levels, more severe tubular damage, and elevated expression of Kim1 and Ngal genes in the kidney in comparison with WT mice. Moreover, the transcriptomic analysis revealed augmented inflammatory response in the kidneys of Tet2−/− mice. Conclusions Tet2 is dispensable for kidney development and function at baseline condition while protects against renal IR injury possibly through repressing inflammatory response. Our findings suggest that Tet2 may be a potential target for the intervention of IR-induced acute kidney injury (AKI).
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Renal function
Kidney development
Gene Expression
Ischemia-reperfusion injury
Kidney
Dioxygenases
Adherens junction
03 medical and health sciences
Cytosine
Mice
Cell junctions
0302 clinical medicine
Lipocalin-2
Internal medicine
Genetics
medicine
Animals
Humans
Hepatitis A Virus Cellular Receptor 1
Molecular Biology
Genetics (clinical)
Tissue homeostasis
Inflammation
Tet2
Chemistry
urogenital system
Research
Acute kidney injury
Inflammatory response
medicine.disease
DNA Demethylation
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
DNA demethylation
Endocrinology
Intercellular Junctions
030220 oncology & carcinogenesis
Renal physiology
Reperfusion Injury
Models, Animal
Developmental Biology
Subjects
Details
- ISSN :
- 18687083
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Clinical epigenetics
- Accession number :
- edsair.doi.dedup.....9a0f1d17ad8f2d955976ea8cbbec9116