Knocking down ETS Proto-oncogene 1 (ETS1) alleviates the pyroptosis of renal tubular epithelial cells in patients with acute kidney injury by regulating the NLR family pyrin domain containing 3 (NLRP3) transcription

Juan, Chenxia; Zhu, Ye; Chen, Yan; Mao, Yan Ping; Zhou, Yan; Zhu, Weiwei; Wang, Xufang; Wang, Qian

doi:10.1080/21655979.2022.2079242

Cited by 7 publications

(5 citation statements)

References 46 publications

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“… 50 In acute kidney injury patients, knocking down ETS1 will alleviate the pyroptosis of renal tubular epithelial cells. 51 In this study, we found that the expression levels of SEPTIN1, CD3G, and ETS1 were up-regulated. Moreover, correlation analysis showed that the expression levels of SEPTIN1, CD3G, and ETS1 were significantly negatively correlated with monocyte abundance.…”

Section: Discussionmentioning

confidence: 51%

Identification of Genes Associated with Decreasing Abundance of Monocytes in Long-Term Peritoneal Dialysis Patients

Zhang,

Jin,

Wang

et al. 2023

IJGM

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Chronic kidney disease (CKD) will become an end-stage renal disease (ESRD) at stage 5. Peritoneal dialysis (PD) is required for renal replacement therapy. This study aims to identify monocytes-related genes in peritoneal cells from long-term PD (LPD) patients and short-term PD (SPD) patients. Methods: Bulk RNA-seq data (GSE125498 dataset) and ScRNA-seq data (GSE130888) were downloaded to identify differentially expressed genes, monocytes-related genes, and monocytes marker genes in LPD patients. Immune infiltration was analyzed in the GSE125498 dataset. Core genes associated with monocytes changes were screened out, followed by functional analysis and expression validation using RT-PCR. Results: Monocytes are the most abundant immune cell in PD. The number of monocytes was remarkably decreased in LPD compared with SPD. A total of 16 up-regulated core genes negatively correlated with the abundance of monocytes were obtained in LPD. The expression of 16 core genes was lower in monocyte clusters than that in other cell clusters. In addition, LCK, CD3G, CD3E, CD3D, and LAT were involved in the signaling pathways of Th1 and Th2 cell differentiation, T cell receptor signaling pathway, and Th17 cell differentiation. CD2 was involved in hematopoietic cell lineage signaling pathway. Conclusion: Identification of monocytes related-genes and related signaling pathways could be helpful in understanding the molecular mechanism of monocytes changes during PD.

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Section: Discussionmentioning

confidence: 51%

Identification of Genes Associated with Decreasing Abundance of Monocytes in Long-Term Peritoneal Dialysis Patients

Zhang,

Jin,

Wang

et al. 2023

IJGM

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“…Therefore, we screened the up-regulated TFs in SCI which could regulate NLRP3/PRGs, to find potential targets for inhibiting SCI pyroptosis. A total of 39 TFs were screened out, 16 of which have been reported to be involved in regulating pyroptosis: ERG ( Yao et al, 2022 ), FLI1 ( Li et al, 2018 , 2019 ), FOXM1 ( Xu et al, 2021 ), HIC1 ( Gao et al, 2021 ), JUN ( Wang et al, 2020 ), KLF4 ( Xiong et al, 2021 ), USF2 ( Sun et al, 2022 ), STAT2 ( Wang et al, 2022 ), FOS ( Wang et al, 2021 ), NFATC1 ( Kai et al, 2020 ), MYC ( Gaikwad et al, 2020 ), NFE2L2 ( Ling et al, 2021 ), SMAD3 ( Zhu et al, 2020 ), ETS1 ( Juan et al, 2022 ), IKZF1 ( Kadono et al, 2022 ), and HMGA1 ( Liang et al, 2022 ). In addition, we performed KEGG Pathway Analysis on these 39 TFs, which were enriched into multiple signaling pathways, such as MAPK signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway, and Toll-like receptor signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Identification of canonical pyroptosis-related genes, associated regulation axis, and related traditional Chinese medicine in spinal cord injury

Shan

Yin

2023

Front. Aging Neurosci.

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Neuroinflammation plays an important role in spinal cord injury (SCI), and pyroptosis is inflammatory-related programmed cell death. Although neuroinflammation induced by pyroptosis has been reported in SCI, there is a lack of systematic research on SCI pyroptosis and its regulation mechanism. The purpose of this study was to systematically analyze the expression of pyroptosis-related genes (PRGs) in different SCI models and associated regulation axis by bioinformatics methods. We downloaded raw counts data of seven high-throughput sequencings and two microarray datasets from the GEO database, classified by species (rat and mouse) and SCI modes (moderate contusive model, aneurysm clip impact-compression model, and hemisection model), including mRNAs, miRNAs, lncRNAs, and circRNAs, basically covering the acute, subacute and chronic stages of SCI. We performed differential analysis by R (DEseq2) or GEO2R and found that the AIM2/NLRC4/NLRP3 inflammasome-related genes, GSDMD, IL1B, and IL18, were highly expressed in SCI. Based on the canonical NLRP3 inflammasome-mediated pyroptosis-related genes (NLRP3/PRGs), we constructed transcription factors (TFs)–NLRP3/PRGs, miRNAs- Nlrp3/PRGs and lncRNAs/circRNAs/mRNAs–miRNA- Nlrp3/PRGs (ceRNA) networks. In addition, we also predicted Traditional Chinese medicine (TCM) and small, drug-like molecules with NLRP3/PRGs as potential targets. Finally, 39 up-regulated TFs were identified, which may regulate at least two of NLRP3/PRGs. A total of 7 down-regulated miRNAs were identified which could regulate Nlrp3/PRGs. ceRNA networks were constructed including 23 lncRNAs, 3 cicrRNAs, 6 mRNAs, and 44 miRNAs. A total of 24 herbs were identified which may with two NLRP3/PRGs as potential targets. It is expected to provide new ideas and therapeutic targets for the treatment of SCI.

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“…Knocking down C/EBPβ inhibits the NLRP3 inflammasome-mediated Caspase-1 signaling pathway by inactivating the TFAM/advanced glycation end-products pathway. The interaction of C/EBPβ and TFAM promotes pyroptosis by activating the NLRP3/Caspase-1 signaling axis, thereby promoting the occurrence of AKI [64]. TRAF-interacting protein with forkhead-associated domain is also involved in pyroptosis by activating mitochondrial damage and may be a therapeutic target to treat SA-AKI [43].…”

Section: Ischemia-reperfusion Injury Akimentioning

confidence: 99%

“…Transcription factors may also play an essential role in the signaling pathway in the regulation of pyroptosis. For instance, ETS Proto-Oncogene 1 (ETS1), a transcription factor, can bind to the upstream promoter transcription site of NLRP3 and trans-activate the NLRP3 of RTEC, knockdown of ETS1 significantly inhibits pyroptosis [ 63 ]. Similarly, in LPS/ATP-induced HK-2 cells, the enhancer binding protein β (C/EBPβ) or mitochondrial transcription factor A (TFAM) is upregulated, knocking down C/EBPβ inhibits LPS combined with ATP-induced cell damage and the secretion of IL-1β and IL-18.…”

Section: Ischemia-reperfusion Injury Akimentioning

confidence: 99%

Pyroptosis: The Determinator of Cell Death and Fate in Acute Kidney Injury

Xiong,

Zhao

2023

Kidney Dis

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Background: Acute kidney injury (AKI) is kidney damage that leads to a rapid decline in function. AKI primarily occurs when the tubular epithelium is damaged, causing swelling, loss of brush margin, and eventual apoptosis. Research has shown that tubular epithelial cell damage in AKI is linked to cell cycle arrest, autophagy, and regulation of cell death. Summary: Pyroptosis, a type of programmed cell death triggered by inflammation, is believed to play a role in the pathophysiology of AKI. Cumulative evidence has shown that pyroptosis is the main cause of tubular cell death in AKI. Thus, targeted intervention of pyroptosis may be a promising therapeutic approach for AKI. In this review, we delve deep into the cutting-edge research surrounding pyroptosis in the context of AKI, shedding light on its intricate mechanisms and potential implications for clinical practice. Additionally, we explore the exciting realm of potential pre-clinical treatment options for AKI, aiming to pave the way for future therapeutic advancements. Key Messages: Pyroptosis, a highly regulated form of cell death, plays a crucial role in determining the fate of cells during the development of AKI. This intricate process involves the activation of inflammasomes, which are multi-protein complexes that initiate pyroptotic cell death. By understanding the mechanisms underlying pyroptosis, researchers aim to gain insights into the pathogenesis of AKI and potentially identify new therapeutic targets for this condition.

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Knocking down ETS Proto-oncogene 1 (ETS1) alleviates the pyroptosis of renal tubular epithelial cells in patients with acute kidney injury by regulating the NLR family pyrin domain containing 3 (NLRP3) transcription

Cited by 7 publications

References 46 publications

Identification of Genes Associated with Decreasing Abundance of Monocytes in Long-Term Peritoneal Dialysis Patients

Identification of Genes Associated with Decreasing Abundance of Monocytes in Long-Term Peritoneal Dialysis Patients

Identification of canonical pyroptosis-related genes, associated regulation axis, and related traditional Chinese medicine in spinal cord injury

Pyroptosis: The Determinator of Cell Death and Fate in Acute Kidney Injury

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