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Hsa_circ_0001162 Inhibition Alleviates High Glucose-Induced Human Podocytes Injury by the miR-149-5p/MMP9 Signaling Pathway

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Abstract

Emerging evidences suggested that circular RNAs (circRNAs) are involved in diabetic nephropathy (DN). Accumulating evidence had suggested that the degree of podocyte is a major prognostic determinant of DN progression. However, the function and in-depth mechanisms of hsa_circ_0001162 in podocyte injury of DN remain unclear. Hsa_circ_0001162 expression was detected by real-time quantitative PCR (RT-qPCR) in peripheral blood of DN patients and high glucose-induced podocytes injury model. The cell counting kit 8, 5-ethynyl-2'-deoxyuridine, flow cytometry with Annexin V-FITC/PI staining, caspase-3 activity assay Kit, enzyme linked immunosorbent assay (ELISA), RT-qPCR and western blotting were used to evaluate the effect of hsa_circ_0001162 / miR-149-5p / MMP9 axis on high glucose-induced podocyte injury. Mechanistically, dual luciferase reporter was used to confirm the relationship of miR-149-5p and hsa_circ_0001162 or MMP9. Furthermore, RNA-pull down and immunoprecipitation assay were implemented to verify the potential regulatory effects of EIF4A3 on biogenesis of hsa_circ_0001162. Our results showed that hsa_circ_0001162 was highly expressed in peripheral blood of DN patients and high glucose-induced podocytes injury model, and the knockdown of hsa_circ_0001162 increased the proliferation, inhibited the apoptosis, and suppressed inflammatory response in high glucose-induced podocytes injury. Mechanism studies demonstrated that EIF4A3 bound with flanking sequences of hsa_circ_0001162 to promote hsa_circ_0001162 expression, upregulated hsa_circ_0001162 increased the MMP9 expression via sponging miR-149-5p, thus aggravating the high glucose-induced podocytes injury. Overall, our data demonstrated that knockdown of hsa_circ_0001162 inhibited high glucose-induced podocytes injury by regulating miR-149-5p/MMP9 axis, and intervention of hsa_circ_0001162/miR-149-5p/MMP9 axis may be a potentially promising therapeutic strategy for podocyte injury in DN patients.

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Data Availability

The data used to support the findings of this study are available from the corresponding author, upon reasonable request.

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Funding

This work was supported by Shenzhen Science and Technology Innovation Commission Fund of 2022 (grant number: JCYJ20220530141600002) and Shenzhen Science and Technology Innovation Commission Fund of 2021 (grant number: JCYJ20210324112408022).

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  1. Department of Nephrology, Shenzhen Nanshan People’s Hospital and The 6Th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, China

    Ling Ye, Jie-hui Chen, Sheng-lang Zhu, Dan-dan Xu, Yun Yang & Ming-pei Shi

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  1. Ling Ye
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Contributions

Ling Ye and Shenglang Zhu contributed to the study conception and design. Material preparation and data collection and analysis were performed by Jiehui Chen, Dandan Xu, Ling Ye, Shenglang Zhu, Yun Yang, and Mingpei Shi. The first draft of the manuscript was written by Ling Ye and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ling Ye.

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This study was approved by the Ethics Committee of Huazhong University of Science and Technology Union Shenzhen Hospital (No. LW-2022–004) and peforemed in accordance with the principles of the Declaration of Helsinki.

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Ye, L., Chen, Jh., Zhu, Sl. et al. Hsa_circ_0001162 Inhibition Alleviates High Glucose-Induced Human Podocytes Injury by the miR-149-5p/MMP9 Signaling Pathway. Appl Biochem Biotechnol 195, 7255–7276 (2023). https://doi.org/10.1007/s12010-023-04431-y

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