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Mechanism of miR-365 in regulating BDNF-TrkB signal axis of HFD/STZ induced diabetic nephropathy fibrosis and renal function

  • Nephrology - Original Paper
  • Published:
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Abstract

Purpose

Diabetic nephropathy (DN) is one of the most serious complications of diabetes that leads to decline of renal function. Although numerous studies have revealed that microRNAs (miRNAs) play essential roles in the progression of DN, whether miR-365 is involved remains elusive.

Methods

The successful construction of DN model was confirmed by ELSIA, hematoxylin–eosin (HE) and Masson staining assay. The expression of miR-365 was detected through RT-qPCR. The levels of BDNF, p-TrkB, α-smooth muscle actin (SMA), collagen IV (Col.IV), transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were evaluated by western blot, IF or ELISA assays. Luciferase reporter assay was used to detect the interaction between miR-365 and BDNF.

Results

The DN mice model was induced by streptozotocin (STZ). Then miR-365 expression was found to upregulate in tissues of DN rat. Furthermore, elevated expression of miR-365 was found in high glucose (HG)-treated HK-2 cells. Silencing of miR-365 suppressed the accumulation of ECM components and secretion of inflammatory cytokines in HK-2 cells. In addition, it was demonstrated that miR-365 could target BDNF. The protein levels of BDNF and p-TrkB were negatively regulated by miR-365 in HK-2 cells. Moreover, inhibition of miR-365 suppressed the levels of SMA, Col.IV, TGF-β1, TNF-α, and IL-6, indicating the renal fibrosis was inhibited by miR-365 knockdown.

Conclusion

MiR-365 could regulate BDNF-TrkB signal axis in STZ induced DN fibrosis and renal function. The results of the current study might provide a promising biomarker for the treatment of DN in the future.

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Availability of data and material

All data generated or analyzed during this study are included in this published article, so the code availability is not applicable.

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Funding

This research was supported by the Zhejiang Health Science and Technology Project (2021KY1130).

Author information

Author notes

  1. Peng Zhao and Xiaqiu Li contributed to this work equally.

Authors and Affiliations

  1. Department of Nephrology, Haining People’s Hospital, No. 2, Qianjiang West Road, Haizhou Street, Haining, 314400, Zhejiang, China

    Peng Zhao, Xiaqiu Li & Yu Sun

  2. Department of General Medicine, Haining People’s Hospital, Haining, 314400, Zhejiang, China

    Yang Li

  3. Department of Endocrinology, Haining People’s Hospital, Haining, 314400, Zhejiang, China

    Jiaying Zhu

  4. Department of Endocrinology, Hengdian Wenrong Hospital, 99 Yingbin Road, Dongyang, 322118, Zhejiang, China

    Jianli Hong

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  1. Peng Zhao
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Contributions

PZ: methodology, software, validation, and data curation. XL: methodology, software, validation, and writing-original draft. YL: software, validation, and methodology. JZ: software, methodology, and writing—review and editing. YS: conceptualization, methodology, investigation, and supervision. JH: conceptualization, methodology, investigation, and supervision. All authors read and approved the final manuscript.

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Correspondence to Yu Sun or Jianli Hong.

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The experiments involved in animals were performed according to the National Institutes of Health guide for the care and use of Laboratory animals.

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Zhao, P., Li, X., Li, Y. et al. Mechanism of miR-365 in regulating BDNF-TrkB signal axis of HFD/STZ induced diabetic nephropathy fibrosis and renal function. Int Urol Nephrol 53, 2177–2187 (2021). https://doi.org/10.1007/s11255-021-02853-3

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  • DOI: https://doi.org/10.1007/s11255-021-02853-3

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