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Circ_0060077 Knockdown Alleviates High-Glucose-Induced Cell Apoptosis, Oxidative Stress, Inflammation and Fibrosis in HK-2 Cells via miR-145-5p/VASN Pathway

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Abstract

The involvement of circular RNAs (circRNAs) in the progression of diabetic nephropathy (DN) has been reported. However, the functions of circ_0060077 in DN remain unclear. HK-2 cells were treated with high glucose (HG) to establish DN cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) was proceeded to determine the levels of circ_0060077, microRNA-145-5p (miR-145-5p) and vasorin (VASN). Cell counting kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) assay and colony formation assay were conducted to assess cell proliferation ability. Flow cytometry analysis was employed for cell apoptosis. The oxidative stress level was evaluated by commercial kits. Enzyme-linked immunosorbent assay (ELISA) was adopted to examine the concentrations of inflammatory factors. Western blot assay was utilized for protein levels. Dual-luciferase reporter assay and RNA pull-down assay were manipulated to analyze the relationships among circ_0060077, miR-145-5p and VASN. Circ_0060077 level was increased in DN patients and HG-stimulated HK-2 cells. Circ_0060077 knockdown ameliorated the inhibitory effect of HG on HK-2 cell proliferation and the promotional effects on cell apoptosis, oxidative stress, inflammation and fibrosis. MiR-145-5p was identified as the target for circ_0060077 and miR-145-5p inhibition ameliorated the effect of circ_0060077 silencing on HG-induced HK-2 cell injury. Moreover, miR-145-5p directly bound to VASN. Overexpression of miR-145-5p facilitated cell proliferation and repressed apoptosis, oxidative injury, inflammation and fibrosis in HG-induced HK-2 cells by targeting VASN. Circ_0060077 silencing protected HK-2 cells from HG-induced damage by regulating miR-145-5p/VASN axis.

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Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang City, Henan Province, China

    Jinjin Zhou, Xia Peng, Yanhai Ru & Jiayun Xu

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  1. Jinjin Zhou
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  2. Xia Peng
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Contributions

Jinjin Zhou participated in the design of the work, methodology, data interpretation, and analysis for the work, carried out the statistical analysis and drafted the manuscript. Xia Peng participated in the methodology, data interpretation and analysis for the work. Yanhai Ru and Jiayun Xu participated in data interpretation and methodology. All authors read and approved the final manuscript.

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Correspondence to Jiayun Xu.

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The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration and has been approved by the Ethics Committee of The First Affiliated Hospital of Henan University of Science and Technology.

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The original online version of this article was revised: The corresponding author of this article should be Jiayun Xu, jiayunxu23560@163.com.

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Zhou, J., Peng, X., Ru, Y. et al. Circ_0060077 Knockdown Alleviates High-Glucose-Induced Cell Apoptosis, Oxidative Stress, Inflammation and Fibrosis in HK-2 Cells via miR-145-5p/VASN Pathway. Inflammation 45, 1911–1923 (2022). https://doi.org/10.1007/s10753-022-01649-6

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