Programmed Cell Death in Sepsis Associated Acute Kidney Injury

Abstract

Sepsis-associated acute kidney injury (SA-AKI) is common in patients with severe sepsis, and has a high incidence rate and high mortality rate in ICU patients. Most patients progress to AKI before drug treatment is initiated. Early studies suggest that the main mechanism of SA-AKI is that sepsis leads to vasodilation, hypotension and shock, resulting in insufficient renal blood perfusion, finally leading to renal tubular cell ischemia and necrosis. Research results in recent years have shown that programmed cell death such as apoptosis, necroptosis, pyroptosis and autophagy play important roles. In the early stage of sepsis-related AKI, autophagy bodies form and inhibit various types of programmed cell death. With the progress of disease, programmed cell death begins. Apoptosis promoter represents caspase-8-induced apoptosis and apoptosis effector represents caspase-3-induced apoptosis, however, caspase-11 and caspase-1 regulate gasdermin D-mediated pyroptosis. Caspase-8 and receptor interacting kinase 1 bodies mediate necroptosis. This review focuses on the pathophysiological mechanisms of various programmed cell death in sepsis-related AKI.

Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4

“…Autophagy-mediated lysosomal degradation and the ubiquitin proteasome system are two major pathways that maintain intracellular homeostasis by removing damaged organelles and misfolded proteins ( Xu et al, 2020 ). Selective autophagy also regulates ferroptosis by degrading GPX4 ( Wu et al, 2022 ). Therefore, the co-targeting of autophagy and GPX4 could function synergistically to kill BC cells ( Sun et al, 2021b ).…”

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

“…It has been reported that inflammatory factors can directly promote apoptosis, further aggravating sepsis-induced lung injury 26 . In addition, pyroptosis has been thought to be involved in septic ALI [27][28][29] . Therefore, this study focused on exploring the effects of circPTK2 on pyroptosis and inflammation in septic ALI.…”

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

“…Necroptosis-related apoptosis is morphologically distinct from apoptosis, which is closely associated with inflammation [ 65 ] and is characterized by rupture of the plasma membrane, leakage of cell contents, and swelling of organelles. [ 66 ] Necroptosis is not dependent on cystathionine but is regulated through the involvement of multiple cellular signaling proteins, including receptor-interacting protein kinase 1, receptor-interacting protein kinase 3 (RIPK3) and its downstream target, and the mixed-spectrum kinase structural domain (MLKL). [ 67 ] Many cellular mediators can activate necrotrophic apoptotic pathways such as death receptors, interferons, toll-like receptors and RNA or DNA sensors.…”