MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway

Abstract

Renal ischemia-reperfusion injury (IRI) is one of the underlying causes of acute kidney injury and also an unavoidable problem in renal transplantation. Lots of miRNAs and targets have been found to participate in some post-transcriptional processes in renal IRI, however, the detailed knowledge of miRNA targets and mechanism is unknown. In this study, miR-124 was found inhibited and PARP1 was overexpressed in renal IRI cells and mouse models. Dual-luciferase reporter assay revealed that miR-124 post-transcriptionally regulated PAPR1 3′UTR activity. Our results also demonstrated miR-124 negatively regulated PARP1 which played a role in necroptosis of renal ischemia-reperfusion injury by activating TNFα. TNFα induced the RIP1/RIP3 necroptosis signaling pathway to aggravate the renal injury. Collectively, these studies identified PARP1 as a direct target of miR-124 and activated RIP1/RIP3 necroptosis signaling pathway through TNFα. It elucidated the protective effect of miR-124 in renal ischemia-reperfusion injury, which demonstrated the regulatory mechanism of miR-124/PARP1 in renal injury and exhibited the potential as a novel therapeutic for the treatment of renal IRI.

ADAMTS7-Mediated Complement Factor H Degradation Potentiates Complement Activation to Contributing to Renal Injuries

“…As we previously reported that ADAMTS7 was upregulated after H 2 O 2 and proinflammatory cytokine stimuli, 32 ADAMTS7 upregulation in both models was possibly due to oxidative stress and inflammatory response, which mediated the pathogenesis of SLE and renal I/R injury. [33][34][35][36][37] Moreover, we demonstrated that ADAMTS7 deficiency rescued CFH degradation and alleviated complement-mediated renal pathologies, but without affecting complement-dependent serum bactericidal activity. Therefore, ADAMTS7, which degrades CFH, would be a promising anticomplement therapeutic target for related renal injuries, potentially reducing the risk of infection.…”

Role of microRNAs in programmed cell death in renal diseases: A review

“…[ 72 ] Recently, miR-124 was found to attenuate renal IRI by negatively regulating PARP1 through inhibiting the TNFα/RIP1/RIP3 pathway and rescued the miR-124. [ 73 ] MiR-26a-5p alleviated apoptosis by inhibiting the expression of RIP1, RIP3, and MLKL in necrotizing apoptosis. [ 74 ]…”

Interaction Between Intrinsic Renal Cells and Immune Cells in the Progression of Acute Kidney Injury

“…TNF-α has been reported to bind to the TNF receptor 1 on the surface of TECs to induce RIP3-dependent necrotizing apoptosis ( 70 , 71 ). In I/R-induced AKI, TNFα has also been reported to exacerbate kidney injury through the receptor-interacting protein 3(RIP1)/RIP3 necroptosis signaling pathway ( 72 ). Type I interferon α (IFN-α) is a multifunctional active cytokine that induces apoptosis in renal TECs through activation of caspase-3, caspase-8, and caspase-9, leading to DNA fragmentation and nuclear condensation ( 73 ).…”