![]() ![]() ![]() Tonnus W, Meyer C, Steinebach C, Belavgeni A, von Mässenhausen A, Gonzalez NZ, et al. Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation. Thompson ER, Bates L, Ibrahim IK, Sewpaul A, Stenberg B, McNeill A, et al. Microvasculature partial endothelial mesenchymal transition in early posttransplant biopsy with acute tubular necrosis identifies poor recovery renal allografts. Xu-Dubois YC, Ahmadpoor P, Brocheriou I, Louis K, Arzouk Snanoudj N, Rouvier P, et al. Protein kinase C-δ mediates kidney tubular injury in cold storage-associated kidney transplantation. Zhu J, Zhang G, Song Z, Xiang X, Shu S, Liu Z, et al. Reducing ischemic kidney injury through application of a synchronization modulation electric field to maintain Na(+)/K(+)-ATPase functions. In summary, these findings suggest that inhibiting sEV-mediated lncRNA WAC-AS1 secretion and targeting HBP metabolism-induced BACH2 O-GlcNAcylation in renal tubular epithelial cells may serve as new strategies for protecting against graft IRI after kidney transplant.Ĭhen W, Wang L, Liang P, Mast J, Mathis C, Liu CY, et al. The functional and mechanistic regulation of IRI-sEVs was further corroborated in an allograft kidney transplant model and an in situ renal IRI model. Inhibition of sEV biogenesis and secretion by GW4869 and knockout of lncRNA WAC-AS1 in IRI-sEVs both unequivocally diminished the “wave of ferroptosis” propagation and protected against renal allograft IRI. We present the first evidence that intranuclear BACH2 suppresses SLC7A11 and GPX4 transcription by binding to their proximal promoters and decreases cellular anti-peroxidation capability, accordingly facilitating ferroptosis. Additionally, BACH2 O-GlcNAcylation at threonine 389 in renal tubular epithelial cells prominently inhibits its degradation by ubiquitination and promotes importin α5-mediated nuclear translocation. In this study, we decipher a whole new metabolic mechanism underlying ferroptosis and propose a novel spreading pathway of the “wave of ferroptosis” in the renal tissue microenvironment, in which renal IRI cell-secreted small extracellular vesicles (IRI-sEVs) delivering lncRNA WAC-AS1 reprogram glucose metabolism in adjacent renal tubular epithelial cell populations by inducing GFPT1 expression and increasing hexosamine biosynthesis pathway (HBP) flux, and consequently enhances O-GlcNAcylation. The wide propagation of ferroptosis among cell populations in a wave-like manner, developing the “wave of ferroptosis” causes a larger area of tubular necrosis and accordingly aggravates renal allograft IRI. ![]() Ferroptosis is a predominant contributor to renal ischemia reperfusion injury (IRI) after kidney transplant, evoking delayed graft function and poorer long-term outcomes. ![]()
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