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High Glucose-Induced Human Kidney Cell Apoptosis and Inflammatory Injury Are Alleviated by Circ_0008529 Knockdown via Circ_0008529-Mediated miR-485-5p/WNT2B Signaling

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Abstract

Human kidney cell injury is a representative characteristic of diabetic nephropathy (DN), and its development has been shown to be associated with the dysregulation of some circular RNAs (circRNAs). We thus explored the role of circ_0008529 in DN-conditioned human kidney cell injury. Human kidney cells (HK-2) were treated with high glucose (HG) to construct DN models in vitro. Quantitative real-time PCR (qPCR) assay and western blot assay were used for expression detection of circ_0008529, miR-485-5p, and Wnt family member 2B (WNT2B). Cell viability was ascertained by CCK-8 assay. Cell apoptosis was assessed by flow cytometry assay and the expression levels of apoptosis-related markers. The release of inflammatory factors was examined by ELISA. The putative binding relationship between miR-485-5p and circ_0008529 or WNT2B was further verified by dual-luciferase reporter experiment, RIP assay, and pull-down assay. Circ_0008529 was highly expressed in serum of DN patients and HG-treated HK-2 cells. HG largely impaired cell viability and promoted cell apoptosis and inflammation production, while circ_0008529 knockdown attenuated the effects of HG. Circ_0008529 targeted miR-485-5p, and miR-485-5p inhibition recovered HK-2 cell injury that was blocked by circ_0008529 knockdown. In addition, miR-485-5p bound to WNT2B whose expression was positively modulated by circ_0008529. WNT2B overexpression recovered the inhibition of HK-2 cell injury caused by miR-485-5p upregulation. Circ_0008529 targeted the miR-485-5p/WNT2B pathway to regulate HG-induced HK-2 cell apoptosis and inflammatory injury, suggesting that circ_0008529 was a vital regulator in DN development.

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Authors and Affiliations

  1. Department of Nephrology, Xianyang Hospital of Yan’an University, Shaanxi, Xianyang City, China

    Weijun Wang

  2. Department of Stomatology, Ganzhou People’s Hospital, No. 16, Meiguan Avenue, Zhanggong District, Jiangxi, 341000, Ganzhou City, China

    Honghua Lu

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Weijun Wang designed and performed the research; Weijun Wang and Honghua Lu analyzed the data; Weijun Wang wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Honghua Lu.

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The design and performance of this study were approved by Xianyang Hospital of Yan’an University (IRB no. 2020YA112).

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Wang, W., Lu, H. High Glucose-Induced Human Kidney Cell Apoptosis and Inflammatory Injury Are Alleviated by Circ_0008529 Knockdown via Circ_0008529-Mediated miR-485-5p/WNT2B Signaling. Appl Biochem Biotechnol 194, 6287–6301 (2022). https://doi.org/10.1007/s12010-022-04088-z

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