Abstract
BackgroundTen-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.ResultsTet2−/− 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.ConclusionsTet2 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).
Highlights
Ten-eleven translocation (Tet) family methyl-cytosine dioxygenases (Tet1, Ten-eleven translocation 2 (Tet2), and Tet3) are key enzymes to convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) [1,2,3]
We have previously shown that Tet2 is dramatically downregulated in the IR-injured kidney, which is accompanied by a reduction of the global 5hmC level [7]
There was no difference in the morphology and histological structure of kidneys between WT and Tet2−/− groups of mice (Fig. 1a–c)
Summary
Ten-eleven translocation (Tet) family methyl-cytosine dioxygenases (Tet, Tet, and Tet3) are key enzymes to convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) [1,2,3]. Emerging evidence has shown that Tet family genes and 5mC oxidation are critical for embryonic development and the maintenance of adult tissue homeostasis [5]. These above-mentioned studies suggest that Tet family genes as well as 5mC oxidation may play important roles in regulating the physiological and pathophysiological processes in the kidney. The functional importance of Tet gene in the kidney as well as renal IR injury remains unknown. Using a unique Tet2−/− mouse model, Yan et al Clinical Epigenetics (2020) 12:98 here, we determined the impact of Tet deficiency on the function of the kidney at baseline as well as in response to renal IR injury. 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 transcriptomic analysis revealed augmented inflammatory response in the kidneys of Tet2−/− mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
