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CircLARP1B promotes pyroptosis of high glucose-induced renal mesangial cells by regulating the miR-578/TLR4 axis

  • Nephrology - Original Paper
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Abstract

Background

Diabetic nephropathy (DN) is a main cause of end-stage renal disease with high mortality. Circular RNAs (circRNAs) are associated with the pathogenesis of DN. This study aimed to explore the role of circLARP1B in DN.

Methods

The levels of circLARP1B, miR-578, TLR4 in DN and high glucose (HG)-treated cells using quantitative real-time PCR. Their relationship was analyzed using dual-luciferase reporter assay. The biological behaviors were assessed by MTT assay, EDU assay, flow cytometry, ELISA, and western blot.

Results

The results indicated that circLARP1B and TLR4 were highly expressed, and miR-578 was low expressed in patients with DN and HG-induced cells. Knockdown of circLARP1B promoted the proliferation and cell cycle, and inhibited pyroptosis and inflammation of HG-induced cells. CircLARP1B is a sponge of miR-578, which targets TLR4. Rescue experiments showed that inhibition of miR-578 reversed the effects of circLARP1B knockdown, while TLR4 reversed the effects of miR-578.

Conclusion

CircLARP1B/miR-578/TLR4 axis suppressed the proliferation, blocked cell cycle at the G0-G1 phase, promoted pyroptosis, and inflammatory factor release of renal mesangial cells induced by HG. The findings suggested that circLARP1B may be a target for the treatment of DN.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by Xi’an Science and Technology Planning Project Medical Research Project: General Research under grant number 2023JH-YXYB-0302.

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Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Xi’an Medical University, Xi’an, China

    Yan Du

  2. Department of Clinical Pharmacy, The First Affiliated Hospital of Xi’an Medical University, Xi’an, China

    Yu Feng

  3. Department of General Surgery, The First Affiliated Hospital of Xi’an Medical University, No. 48, Fenghao West Road, Lianhu District, Xi’an, 710077, Shaanxi, China

    Yu Cai

  4. Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, China

    Chang Tian

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  1. Yan Du
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  2. Yu Feng
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  3. Yu Cai
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  4. Chang Tian
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Contributions

All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript. YD drafted the work and revised it critically for important intellectual content; YF was responsible for the acquisition, analysis and interpretation of data for the work; YC and CT made substantial contributions to the conception or design of the work.

Corresponding authors

Correspondence to Yu Cai or Chang Tian.

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The authors declare that they have no competing interests.

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The study was approved by the Ethics Committee of The First Affiliated Hospital of Xi’an Medical University.

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Du, Y., Feng, Y., Cai, Y. et al. CircLARP1B promotes pyroptosis of high glucose-induced renal mesangial cells by regulating the miR-578/TLR4 axis. Int Urol Nephrol 56, 283–293 (2024). https://doi.org/10.1007/s11255-023-03672-4

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  • DOI: https://doi.org/10.1007/s11255-023-03672-4

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