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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.

ABSTRACT: Acute kidney injury (AKI) has a high mortality rate, but its pathogenesis remains unclear Lipopolysaccharide (LPS)-mediated renal tubular epithelial pyroptosis is involved in the pathogenesis of AKI. NLR family of pyrin domains containing 3 (NLRP3) plays an important role in pyroptosis. To further understand the transcriptional regulation mechanism of NLRP3, the peripheral blood of patients with AKI was analyzed in this study, showing that the levels of NLRP3 and cell pyroptosis in patients with AKI were significantly higher than those in normal controls. Furthermore, elevated levels of NLRP3 and cell pyroptosis were found in renal tubular epithelial cells after LPS treatment. Transcription factor ETS Proto-Oncogene 1 (ETS1) could bind to the upstream promoter transcription site of NLRP3 to transactivate NLRP3 in renal tubular epithelial cells. The cell pyroptosis level also decreased by knocking down ETS1. It is concluded that knocking down of ETS1 may reduce the renal tubular epithelial pyroptosis by regulating the transcription of NLRP3, thus relieving AKI. ETS1 is expected to be a molecular target for the treatment of AKI.

SUBMITTER: Juan C

PROVIDER: S-EPMC9275905 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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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.

Juan Chenxia C Zhu Ye Y Chen Yan Y Mao Yan Y Zhou Yan Y Zhu Weiwei W Wang Xufang X Wang Qian Q

Bioengineered 20220501 5

Acute kidney injury (AKI) has a high mortality rate, but its pathogenesis remains unclear Lipopolysaccharide (LPS)-mediated renal tubular epithelial pyroptosis is involved in the pathogenesis of AKI. NLR family of pyrin domains containing 3 (NLRP3) plays an important role in pyroptosis. To further understand the transcriptional regulation mechanism of NLRP3, the peripheral blood of patients with AKI was analyzed in this study, showing that the levels of NLRP3 and cell pyroptosis in patients with ...[more]

PMID: 35611792

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Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is a highly lethal malignancy with poor prognosis. Polypeptide N-acetylgalactosaminyltransferase-6 (GALNT6) is frequently overexpressed in PDAC. However, the role of GALNT6 in the PDAC remains unclear.MethodsThe expression of GALNT6 in pancreatic cancer and normal tissues were analyzed by bioinformatic analyses and immunohistochemistry. CCK8 and colony formation were used to detect cell proliferation. Flow cytometry was applied to detect cell cycle.The pyroptosis was detected by scanning electron microscopy. The mRNA expression was detected by qRT-PCR. The protein expression and localization were detected by western blot and immunofluorescence assay. ELISA was used to detect the levels of inflammatory factors.ResultsThe expression of GALNT6 was associated with advanced tumor stage, and had an area under curve (AUC) value of 0.919 in pancreatic cancer based on the cancer genome atlas (TCGA) dataset. Knockdown of GALNT6 inhibited cell proliferation, migration, invasion and cell cycle arrest of PDAC cells. Meanwhile, knockdown of GALNT6 increased the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18), the release of inflammasome and an increasing of Gasdermin D (GSDMD), N-terminal of GSDMD (GSDMD-N), Gasdermin E (GSDME) and N-terminal of GSDME (GSDME-N) in PDAC cells. GALNT6 suppressed the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and GSDMD by glycosylation of NF-κB and inhibiting the nucleus localization of NF-κB. Additionally, GALNT6 promotes the degradation of GSDME by O-glycosylation.ConclusionWe found that GALNT6 is highly expressed in pancreatic cancer and plays a carcinogenic role. The results suggested that GALNT6 regulates the pyroptosis of PDAC cells through NF-κB/NLRP3/GSDMD and GSDME signaling. Our study might provides novel insights into the roles of GALNT6 in PDAC progression.

Dataset Information

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.

Publications

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.

Similar Datasets

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