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A Novel MIR503HG/miR-497-5p/CCL19 Axis Regulates High Glucose-Induced Cell Apoptosis, Inflammation, and Fibrosis in Human HK-2 Cells

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Abstract

Long non-coding RNAs (lncRNAs) play crucial roles in the development of diabetic nephropathy (DN). Here, we explored the activity and mechanism of MIR503 host gene (MIR503HG) in high glucose (HG)-evoked cytotoxicity in HK-2 cells. MIR503HG, microRNA (miR)-497-5p, and C–C motif chemokine ligand 19 (CCL19) were quantified by quantitative real-time PCR (qRT-PCR) and western blot. The direct relationship between miR-497-5p and MIR503HG or CCL19 was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell viability and apoptosis were evaluated by XTT assay and flow cytometry, respectively. Our data showed that MIR503HG was overexpressed in HG-stimulated HK-2 cells. Knockdown of MIR503HG alleviated HG-evoked cell apoptosis, inflammation, and fibrosis in HK-2 cells. Mechanistically, MIR503HG regulated miR-497-5p expression via a binding site. MIR503HG depletion reduced HG-evoked cell apoptosis, inflammation, and fibrosis in HK-2 cells by up-regulating miR-497-5p. Moreover, miR-497-5p directly targeted and suppressed CCL19. MiR-497-5p-mediated suppression of CCL19 relieved HG-induced cell apoptosis, inflammation, and fibrosis in HK-2 cells. Furthermore, MIR503HG regulated CCL19 expression via miR-497-5p competition. Our findings identify a new MIR503HG/miR-497-5p/CCL19 network in the regulating HG-evoked cell apoptosis, inflammation, and fibrosis in HK-2 cells.

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Authors and Affiliations

  1. Department of Nephrology, Wenling First People’s Hospital of Zhejiang Province, No.333 Chuan’an South Road, Chengxi Street, Wenling City, 317500, Zhejiang, China

    Danping Zhang, Xiaoxiao Chen & Dan Zheng

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  1. Danping Zhang
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  2. Xiaoxiao Chen
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  3. Dan Zheng
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Danping Zhang designed and performed the research; Danping Zhang, Xiaoxiao Chen, and Dan Zheng analyzed the data; Danping Zhang wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Dan Zheng.

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Zhang, D., Chen, X. & Zheng, D. A Novel MIR503HG/miR-497-5p/CCL19 Axis Regulates High Glucose-Induced Cell Apoptosis, Inflammation, and Fibrosis in Human HK-2 Cells. Appl Biochem Biotechnol 194, 2061–2076 (2022). https://doi.org/10.1007/s12010-021-03776-6

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