Ten-eleven translocation methyl-cytosine dioxygenase 2 deficiency exacerbates renal ischemia-reperfusion injury

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 ofTet2andTet3genes are relatively abundant in the adult murine kidneys whileTet1gene 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 ofKim1andNgalgenes in the kidney in comparison with WT mice. Moreover, the transcriptomic analysis revealed augmented inflammatory response in the kidneys ofTet2(-/-)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).