Background and Objective: Acute kidney injury (AKI) is a complication of sepsis. Pyroptosis of gasdermin D (GSDMD)-mediated tubular epithelial cells (TECs) play important roles in pathogenesis of sepsis-associated AKI. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3), an imprinted gene involved in tumorigenesis, is implicated in pyroptosis occurring in multiple organs. Herein, we investigated the role and mechanisms of MEG3 in regulation of TEC pyroptosis in lipopolysaccharide (LPS)-induced AKI.Materials and Methods: Male C57BL/6 mice and primary human TECs were treated with LPS for 24 h to establish the animal and cell models, respectively, of sepsis-induced AKI. Renal function was assessed by evaluation of serum creatinine and urea levels. Renal tubule injury score was assessed by Periodic acid-Schiff staining. Renal pyroptosis was assessed by evaluating expression of caspase-1, GSDMD, and inflammatory factors IL-1β and IL-18. Cellular pyroptosis was assessed by analyzing the release rate of LDH, expression of IL-1β, IL-18, caspase-1, and GSDMD, and using EtBr and EthD2 staining. MEG3 expression in renal tissues and cells was detected using RT-qPCR. The molecular mechanisms of MEG3 in LPS-induced AKI were assessed through bioinformatics analysis, RNA-binding protein immunoprecipitation, dual luciferase reporter gene assays, and a rescue experiment.Results: Pyroptosis was detected in both LPS-induced animal and cell models, and the expression of MEG3 in these models was significantly up-regulated. MEG3-knockdown TECs treated with LPS showed a decreased number of pyroptotic cells, down-regulated secretion of LDH, IL-1β, and IL-18, and decreased expression of GSDMD, compared with those of controls; however, there was no difference in the expression of caspase-1 between MEG3 knockdown cells and controls. Bioinformatics analysis screened out miR-18a-3P, and further experiments demonstrated that MEG3 controls GSDMD expression by acting as a ceRNA for miR-18a-3P to promote TECs pyroptosis.Conclusion: Our study demonstrates that lncRNA MEG3 promoted renal tubular epithelial pyroptosis by regulating the miR-18a-3p/GSDMD pathway in LPS-induced AKI.

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.

Coronavirus disease 2019 (COVID‐19) can cause damage to multiple organ, not only to the lungs, but also to the kidneys. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can cause acute and chronic kidney disease through direct viral infection, indirect injury, and vaccination‐related injury. Like lung injury, kidney injury is also an important aspect affecting the severity and prognosis of SARS‐CoV‐2. This article summarizes the pathogenesis, pathological manifestations, and clinical features of SARS‐CoV‐2 direct or indirect renal injury. Including direct injury, indirect injury, special comorbidities (receiving kidney transplantation and chronic kidney disease), and vaccine‐related renal injury, and exploring the possible therapeutic effect of anti‐SARS‐CoV‐2 therapy on renal injury. The purpose is to provide reference for understanding COVID‐19‐related renal injury, guiding clinical and pathological diagnosis and treatment, and evaluating prognosis.

A growing number of studies have confirmed that immune cells play various key roles in the pathophysiology of acute kidney injury (AKI) development. After the resident immune cells and intrinsic renal cells are damaged by ischemia and hypoxia, drugs and toxins, more immune cells will be recruited to infiltrate through the release of chemokines, while the intrinsic cells promote macrophage polarity conversion, and the immune cells will promote various programmed deaths, phenotypic conversion and cycle arrest of the intrinsic cells, ultimately leading to renal impairment and fibrosis. In the complex and dynamic immune microenvironment of AKI, the bidirectional interaction between immune cells and intrinsic renal cells affects the prognosis of the kidney and the progression of fibrosis, and determines the ultimate fate of the kidney.

At present, there is no effective drug for the treatment of renal fibrosis; in particular, a safe and effective treatment for renal fibrosis should be established. Cordyceps has several medical effects, including immunoregulatory, antitumor, anti-inflammatory, and antioxidant effects, and may prevent kidney, liver, and heart diseases. Cordyceps has also been reported to be effective in the treatment of renal fibrosis. In this paper, we review the potential mechanisms of Cordyceps against renal fibrosis, focusing on the effects of Cordyceps on inflammation, oxidative stress, apoptosis, regulation of autophagy, reduction of extracellular matrix deposition, and fibroblast activation. We also discuss relevant published clinical trials and meta-analyses. Available clinical studies support the possibility that Cordyceps and related products provide benefits to patients with chronic kidney diseases as adjuvants to conventional drugs. However, the existing clinical studies are limited by low quality and significant heterogeneity. The use of Cordyceps and related products may be a potential strategy for the treatment of renal fibrosis. Randomized controlled trial studies with good methodological quality, favorable experimental design, and large sample size are needed to evaluate the efficacy and safety of Cordyceps.