same-sex mice in .Kidney graft injury and function were evaluated by measuring plasma creatine and BUN levels, PAS staining and cell death (immunofluorescent staining) and GFR values.In male C57BL/6 mice, a newly designed sulfono--AApeptide foldamer, PGB-1 (PP1 gamma binding 1), was administrated to donor kidneys (5 M in University of Wisconsin solution) during cold storage.Syngeneic KTX was conducted after 3 hours of cold storage, and graft injury and function were assessed at 1-and 3-days post-transplantation. Results: We found that deleting PPP1R3G in PTCs significantly enhanced cell viability and reduced tubular cell death.This protective effect was associated with lower activation of necroptosis markers (p-RIP1, p-RIP3, and p-MLKL) and reduced expression of inflammatory factors.In the KTX, PPP1R3G deletion mitigated I/R-induced kidney graft injury, demonstrated by a 51% decrease in plasma creatinine (1.780.16 vs. 0.870.18mg/dL, p<0.001, n=7) and a 55% improvement in GFR in KO mice.Histological analysis showed reduced activated MLKL (p-S345-MLKL) and lower TUNEL staining in KO mice than WT.Additionally, administering PGB-1 to donor kidneys significantly protected grafts from ischemic injury, reducing plasma creatinine by 65% compared to controls.Conclusion: This study demonstrates, for the first time, that Ppp1r3gmediated necroptosis plays a significant role in kidney graft injury during transplantation.Blocking the PPP1R3G/PP1 interaction with PGB-1 effectively halts cell death signaling, highlighting its potential as a therapeutic approach for human KTX.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
Leite et al. (Wed,) studied this question.