Reduction of DNA hydroxymethylation in the mouse kidney insulted by ischemia reperfusion

Mouse model of ischemic acute kidney injury: technical notes and tricks

“…Since the 1960s, various animal models of ischemic AKI have been developed and tested, and currently, two kinds of warm renal ischemia-reperfusion (IR) models are mainly used: 1) bilateral renal ischemic reperfusion (IR) (2-6, 8, 13, 14, 17, 19, 22, 23, 25-27, 30, 31, 35, 39, 41-43, 46, 51, 53-57, 59, 61, 63, 67, 68, 75-80) and 2) unilateral renal IR (1,9,15,18,20,21,24,29,33,34,37,38,40,44,50,58,60,62,64,66). Depending on whether the contralateral kidney is removed, the unilateral model can be further divided into two subtypes: unilateral IR with contralateral nephrectomy (15,18,20,29,38,40,44,50) or without contralateral nephrectomy (1,9,21,24,45,60). The bilateral ischemic AKI model is commonly used, because it is considered more relevant to human pathological conditions where blood supply is normally affected in both kidneys (2, 10, 11, 16, 30, 32, 37, 47, 49, 52, 70 -74, 79).…”

5-Hydroxymethylcytosine and disease

“…The mechanism underlying that this pathological process has been investigated extensively, but no relationship between IR and epigenetics was found until 2012, when Huang et al used dot blot, immunochemistry, and hMeDIP-seq methods to show that both global 5hmC and the 5hmC in the proximal promoter regions of the Cxcl10 and Ifngr2 genes were significantly attenuated in the kidneys of IR mice (Fig. 7) [99]. Consistently, the expression of TET1 and TET2 was lower in IR mouse kidneys than in controls, but the expression of 5mC and TET3 was not.…”

Noncoding RNA and epigenetic gene regulation in renal diseases

“…Mehta et al [116] reported that the Calcitonin A (Calca) gene promoter was hypermethylated in cells obtained from the urine of transplant patients with biopsy-proven acute tubular necrosis compared with healthy controls. More recently, levels of the DNA demethylases, Tet1 and Tet2, were found to be downregulated in kidneys that underwent AKI, although a biological role for these enzymes in regulating gene expression during AKI has not yet been demonstrated [117]. We have just begun to understand the robust chromatin modifications that acutely injured kidneys undergo.…”