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CircACTR2 attenuated the effects of tetramethylpyrazine on human kidney cell injury

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Abstract

Tetramethylpyrazine (TMP) is one of the active ingredients of Chuan Xiong that has been reported to have effects on numerous diseases, including diabetic nephropathy (DN). Whereas, related molecular mechanisms are not fully elucidated. We aimed to explore circACTR2’s role in TMP-mediated protective effects on DN. In vitro DN condition was established in human kidney cells (HK-2) by treating high glucose (HG). CCK-8 assay and flow cytometry assay were used to observe cell viability and survival. Oxidative stress was determined by the associated markers using kits. The release of inflammatory factors was detected using ELISA kits. Quantitative real-time PCR (qPCR) and western blot were utilized for expression analysis of cricACTR2, miR-140-5p, and GLI pathogenesis-related 2 (GLIPR2). The binding between miR-140-5p and circACTR2 or GLIPR2 was confirmed by dual-luciferase, RIP, and pull-down studies. HG largely induced HK-2 cell apoptosis, oxidative stress, and inflammation, which were alleviated by TMP. CircACTR2’s expression was enhanced in HG-treated HK-2 cells but attenuated in HG + TMP-treated HK-2 cells. CircACTR2 overexpression attenuated the functional effects of TMP and thus restored HG-induced cell apoptosis, oxidative stress, and inflammation. CircACTR2 bound to miR-140-5p to enhance the expression of GLIPR2. MiR-140-5p restoration or GLIPR2 inhibition reversed the role of circACTR2 overexpression. CircACTR2 attenuated the protective effects of TMP on HG-induced HK-2 cell damages by regulating the miR-140-5p/GLIPR2 network, indicating that circACTR2 was involved in the functional network of TMP in DN.

Highlights

Tetramethylpyrazine alleviated high glucose-induced HK-2 cell injury.

CircACTR2 expression was induced by high glucose but repressed by tetramethylpyrazine.

CircACTR2 overexpression attenuated the effects of tetramethylpyrazine.

CircACTR2 regulated the miR-140-5p/GLIPR2 pathway.

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Data availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of endocrinology, Taihe Hospital of traditional Chinese Medicine, No. 59 Tuanjie West Road, Taihe County, Fuyang, 236600, Anhui, China

    Xiuzhi Chen, Bin Zou & Zhen Yang

Authors
  1. Xiuzhi Chen
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  2. Bin Zou
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  3. Zhen Yang
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Contributions

Conceptualization and Methodology: Bin Zou and Zhen Yang; Formal analysis and Data curation: Xiuzhi Chen and Zhen Yang; Validation and Investigation: Xiuzhi Chen and Bin Zou; Writing - original draft preparation and Writing - review and editing: Xiuzhi Chen, Bin Zou and Zhen Yang; Approval of final manuscript: all authors.

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Correspondence to Xiuzhi Chen.

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The present study was approved by the ethical review committee of Taihe Hospital of traditional Chinese Medicine. Written informed consent was obtained from all enrolled patients.

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Chen, X., Zou, B. & Yang, Z. CircACTR2 attenuated the effects of tetramethylpyrazine on human kidney cell injury. J Bioenerg Biomembr (2024). https://doi.org/10.1007/s10863-024-10001-6

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