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LncRNA 1500026H17Rik knockdown ameliorates high glucose-induced mouse podocyte injuries through the miR-205-5p/EGR1 pathway

  • Nephrology - Original Paper
  • Published:
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Abstract

Background

Podocyte injuries and dysfunctions contribute to the development of diabetic nephropathy (DN). This study aimed to investigate the role and novel mechanism of lncRNA 1500026H17Rik in high glucose (HG)-treated podocytes.

Methods

DN mice were induced by streptozotocin, and DN in vitro models were constructed in mouse podocytes treated with HG. The expression of fibrosis-related proteins and early growth response protein 1 (EGR1) was detected by western blot. The expression of 1500026H17Rik, miR-205-5p and EGR1 mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis was monitored by flow cytometry assay. Oxidative stress was assessed according to the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS). Inflammatory response was assessed according to the releases of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The target relationship between miR-205-5p and 1500026H17Rik or EGR1 was validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay.

Results

1500026H17Rik was upregulated in DN mice and HG-induced podocytes. 1500026H17Rik knockdown alleviated podocyte apoptosis, fibrosis, oxidative stress and inflammation induced by HG. MiR-205-5p was a target of 1500026H17Rik, and EGR1 was a downstream target of miR-205-5p. Rescue experiments presented that miR-205-5p inhibition reversed the effects of 1500026H17Rik knockdown. Moreover, miR-205-5p restoration also ameliorated HG-induced cell injuries, which were overturned by EGR1 overexpression. In addition, EGR1 overexpression recovered podocyte apoptosis, fibrosis, oxidative stress and inflammation weakened by 1500026H17Rik knockdown.

Conclusion

1500026H17Rik knockdown alleviated HG-induced podocyte injuries, including apoptosis, fibrosis, oxidative stress and inflammation, by governing the miR-205-5p/EGR1 pathway, thus involving in DN development.

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Availability of data and materials

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 Nephrology, Zhujiang Hospital of Southern Medical University, No. 253 Industrial Avenue, Haizhu District, Guangzhou, 510280, Guangdong, China

    Jinjin Xia

  2. Department of Nephrology, Tianshui First People’s Hospital, Tianshui, Gansu, China

    Weigang Sun

  3. Medical School of Yangtze University, Jingzhou, Hubei, China

    Jingjing Dun

  4. Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China

    Jinjin Xia

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  1. Jinjin Xia
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  2. Weigang Sun
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Correspondence to Jinjin Xia.

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The present study was approved by the ethical review committee of Zhujiang Hospital of Southern Medical University. Written informed consent was obtained from all enrolled patients.

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Xia, J., Sun, W. & Dun, J. LncRNA 1500026H17Rik knockdown ameliorates high glucose-induced mouse podocyte injuries through the miR-205-5p/EGR1 pathway. Int Urol Nephrol 55, 1045–1057 (2023). https://doi.org/10.1007/s11255-022-03396-x

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