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LncRNA NEAT2 Modulates Pyroptosis of Renal Tubular Cells Induced by High Glucose in Diabetic Nephropathy (DN) by via miR-206 Regulation

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Abstract

Patients suffering from terminal-stage diabetic nephropathy (DN) are commonly diagnosed with kidney failure. The condition of DN patients gets generally improved by long-chain noncoding RNA (LncRNA) since it regulates microRNA (miR). The current study analyzes the role played by NEAT2/miR-206 upon cell death of renal tubular epithelial cells (RTECs), high glucose (HG)-induced inflammation and oxidative stress in diabetic nephropathy (DN). The researcher used high glucose (HG) to treat HK-2 cells in in vitro conditions to establish the DN cell model. qRT-PCR was used to confirm the transfection effect whereas the researcher also tested NEAT2, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing (NLRP3), caspase-1, interleukin IL-1β, gasdermin D (GSMDD)-N, and miR-206. To analyze the proteins in caspase-1, IL-1β, GSMDD-N, and NLRP3, Western blot technique was performed. The technique is also used to observe the pyroptosis. To identify TNF-α, IL-6, MCP-9, NEAT2, miR‐206, and NLRP3, dual‐luciferase reporter assay was conducted through ELISA kit to emphasize the correlation that exists among the above-mentioned factors. NEAT2 has been confirmed to have bound with miR-206 through double luciferase report experiments as well as RNA immunoprecipitation (RIP). NEAT2, present in HK-2 cells, was induced by HG. So, if NEAT2 is knocked down, it would mitigate TNF-α, IL-6, and MCP-9 as well. Among the HK-2 cells intervened with HG, the overexpressed miR-206 that was transfected into cells was in alignment with the modifications introduced in inflammatory factors and cytokines after NEAT2 is knocked down. The current study concludes that if NEAT2 is upregulated, it has the potential to retreat the inhibition of miR-206 on inflammatory response as well pyroptosis. Further, by targeting miR-206, NEAT2 has the potential to enhance HG-induced HK-2 pyroptosis. This miR-206 is predicted to be a latent target in the clinical treatment of DN.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm-Alqura University, Makkah al-Mukarramah, Saudi Arabia

    Amal Ezzat Abd El-Lateef, Adel Galal Ahmed El-Shemi & Mona S. Alhammady

  2. Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

    Amal Ezzat Abd El-Lateef

  3. Department of Pharmacology, Faculty of Medicine, Assiut University, El Fateh, Assiut, Egypt

    Adel Galal Ahmed El-Shemi

  4. Forensic Medicine and Clinical Toxicology Department, Mansoura University, El Gomhouria St, Dakahlia, Egypt

    Mona S. Alhammady

  5. University of Science and Technology of China, Hefei, 230001, Anhui, China

    Rucui Yuan & Yan Zhang

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  1. Amal Ezzat Abd El-Lateef
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  2. Adel Galal Ahmed El-Shemi
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  3. Mona S. Alhammady
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  4. Rucui Yuan
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  5. Yan Zhang
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Correspondence to Rucui Yuan.

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El-Lateef, A.E.A., El-Shemi, A.G.A., Alhammady, M.S. et al. LncRNA NEAT2 Modulates Pyroptosis of Renal Tubular Cells Induced by High Glucose in Diabetic Nephropathy (DN) by via miR-206 Regulation. Biochem Genet 60, 1733–1747 (2022). https://doi.org/10.1007/s10528-021-10164-6

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  • DOI: https://doi.org/10.1007/s10528-021-10164-6

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