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Hsa_circ_0003928 regulates the progression of diabetic nephropathy through miR-136-5p/PAQR3 axis

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Abstract

Background

Diabetic nephropathy (DN) is one of the complications of diabetes and has a high mortality, but its specific pathogenesis is not clear. In recent years, researches on the mechanism of circRNAs in DN have been proved a lot, whereas the functional mechanism of circ_0003928 in DN remains open and it must be investigated to value its important role in DN prevention.

Methods

HK-2 cells were treated with high glucose (HG), normal glucose (NG) or Mannitol. Cell counting kit-8 (CCK8) and 5-ethynyl-2ʹ-deoxyuridine (EdU) assays were performed to detect cell proliferation. Enzyme-linked immunosorbent assay (ELISA) was applied to analyze malondialdehyde (MDA) and superoxide dismutase 1 (SOD) levels. Flow cytometry and western blot were preformed to measure cell apoptosis. Real-time quantitative PCR (RT-qPCR) was used to test the levels of circ_0003928, miR-136-5p and progestin and adipoQ receptor family member 3 (PAQR3) mRNA. Western blot was executed to detect Bcl2 associated X (Bax), B cell leukemia/lymphoma 2 (Bcl2), smooth muscle (αSMA), apolipoprotein (C-IV) and PAQR3 levels. Luciferase reporter assay and RNA pull-down assay were used to analyze the target relationship between miR-136-5p and circ_0003928 or PAQR3.

Results

Circ_0003928 and PAQR3 expression were up-regulated, whereas miR-136-5p was decreased in DN serum and HG-induced HK-2 cells. Circ_0003928 knockdown promoted cell proliferation, and inhibit cell apoptosis, oxidative stress, and fibrosis in HK-2 cells under HG condition. MiR-136-5p silencing overturned the protective effects of si-circ_0003928 on HG-induced HK-2 cells. MiR-136-5p was targeted by circ_0003928 and directly targeted PAQR3. Overexpression of PAQR3 counteracted the inhibitory functions of circ_0003928 knockdown or miR-136-5p overexpression on HG-induced HK-2 cell injury.

Conclusion

Circ_0003928 acted as a sponge of miR-136-5p to up-regulating PAQR3 expression, and then regulate the proliferation, oxidative stress, fibrosis and apoptosis in HG-induced HK-2 cells.

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Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

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Funding

Natural Science Foundation of Shaanxi Province (No. 2021JQ-905) and Talent Support Program of Shaanxi Provincial People’s Hospital (No. 2021JY-31).

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Authors and Affiliations

  1. Kidney Disease and Dialysis Center, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Beilin District, Xi’an, 710068, Shaanxi, China

    W. Zhang, L. Zhang, Q. Dong, X. Wang, Z. Li & Q. Wang

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  1. W. Zhang
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  2. L. Zhang
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  3. Q. Dong
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  4. X. Wang
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  5. Z. Li
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Corresponding author

Correspondence to Q. Wang.

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The authors declare that they have no financial conflicts of interest.

Ethical approval

This study was permitted by the Ethics Committee of Shaanxi Provincial People’s Hospital. No. SPPH-LLBG-17-3.2.

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Written informed consents were obtained from all participants.

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Supplementary Information

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40618_2023_2061_MOESM1_ESM.tif

Supplementary file1 Figure. S1. HG treatment regulated proliferation, oxidative stress, fibrosis and apoptosis in HK-2 cells. HK-2 cells were treated with mannitol, NG, or HG. (A) CCK8 assay was performed to detect cell viability of HK-2 cells; (B, C) The levels of MDA and SOD were analyzed by ELISA assay; (D) EdU assay was performed to analyze cell proliferation; (E) Flow cytometry assay was performed to test cell apoptosis; (F-H) Western blot was performed to analyze Bax and Bcl2 protein levels; (I-K) Western blot was performed to measure αSMA and C-IV protein levels. ***P<0.001. (TIF 2029 KB)

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Zhang, W., Zhang, L., Dong, Q. et al. Hsa_circ_0003928 regulates the progression of diabetic nephropathy through miR-136-5p/PAQR3 axis. J Endocrinol Invest 46, 2103–2114 (2023). https://doi.org/10.1007/s40618-023-02061-z

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  • DOI: https://doi.org/10.1007/s40618-023-02061-z

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