INK4a deletion results in improved kidney regeneration and decreased capillary rarefaction after ischemia-reperfusion injury

Abstract

Lee DH, Wolstein JM, Pudasaini B, Plotkin M. INK4a deletion results in improved kidney regeneration and decreased capillary rarefaction after ischemia-reperfusion injury.

Telomerase, Autophagy and Acute Kidney Injury

“…These results confirmed previous reports that ischemic injury or dysfunctional telomeres induces p16 [14]. p16 protein, a member of the INK4 family (p16 INK4a ), is a cyclin-dependent kinase inhibitor that inhibits the cell cycle by blocking progression from G1 phase to S phase.…”

“…It is a robust biomarker and a possible effector in mammalian renal aging. Deletion of p16 results in improved kidney regeneration and decreased capillary rarefaction after I/R [14]. The mTORC1 inhibitor, rapamycin, partially restored the autophagy response in kidneys following ischemic injury without significant effect on either upregulated p16 or renal tubule epithelial cell proliferation.…”

Sepsis-Associated AKI: Epithelial Cell Dysfunction

“…29 In addition, down-regulation of the CDK inhibitor p16/ INK4a results in improved regeneration after IRI. 30 Although it is well known that PAMPs play a significant role in the generation of sepsis-induced AKI, and that the cell-cycle activation-proliferationarrest phenomenon is a focus of current research, there is still a significant lack of understanding of the processes that link the two together. Our group recently identified insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP2) as superior urine biomarkers for AKI compared with the current canonical markers creatinine, Neutrophil Gelatinase-Associated Lipocalin (NGAL), and Kidney Injury Molecule (KIM) 1, and these markers have been validated clinically.…”

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).…”