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Exosomal circTAOK1 contributes to diabetic kidney disease progression through regulating SMAD3 expression by sponging miR-520h

  • Nephrology - Original Paper
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Abstract

Background

Diabetic nephropathy (DN) is a frequent diabetes complication with complex pathogenesis. Circular RNA (circRNA) circTAOK1 (also named circ_0003928) has been reported to be upregulated in high glucose (HG)-treated human umbilical vein endothelial cells. Also, exosomal circRNAs can exert significant roles in the pathology of various diseases. This study is designed to explore the role and mechanism of exosomal circTAOK1 on the glomerular mesangial cell (GMC) injury in DN.

Methods

Exosomes were detected by a transmission electron microscope. The protein levels of CD9, CD63, proliferating cell nuclear antigen (PCNA), cyclinD1, α-SMA, fibronectin, E-cadherin, N-cadherin, and SMAD family member 3 (SMAD3) were examined by western blot assay. circTAOK1, microRNA-520h (miR-520h), and SMAD3 levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation and cell cycle progression were detected by cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and flow cytometry assays. The binding relationship between miR-520h and circTAOK1 or SMAD3 was predicted by Starbase and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP), RNA pull-down assays.

Results

CircTAOK1 expression was upregulated in the exosomes isolated from HG-treated glomerular epithelial cells (GEC). Moreover, GEC-circTAOK1-Exo could promote proliferation, fibrosis, and epithelial–mesenchymal transition (EMT) of glomerular mesangial cells (GMCs). Mechanically, circTAOK1 could regulate SMAD3 expression by sponging miR-520h, GEO-si-circTAOK1 Exo-induced miR-520h and repressed SMAD3 expression in GMC.

Conclusion

GEC-circTAOK1-Exo could boost proliferation, fibrosis, and EMT of GMC through targeting the miR-520h/SMAD3 axis, providing new insights into the pathogenesis of DN.

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Funding

This work was supported by Science and Technology Talent Cultivation Project of Tianjin Municipal Health Commission (KJ20053).

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Authors and Affiliations

  1. Department of Blood Purification, The Second Hospital of Tianjin Medical University, No. 23 Pingjiang Road, Hexi District, Tianjin, China

    Bo Li, Guijiang Sun, Haibo Yu, Jia Meng & Fang Wei

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11255_2022_3139_MOESM1_ESM.tif

Supplementary file1 Figure S1 Exosome-mediated crcTAOK1 expression is up-regulated in the serum of DN patients. (A) The representative micrograph of round-shaped vesicles using electron microscopy. (B) Western blot for the protein levels of CD9 and CD63 in the exosomes of DN patients. (C) The expression level of exosomal crcTAOK1 using RT-qPCR in serum exosomes from 15 healthy volunteers and 20 DN patients. (D) ROC curve analysis for the diagnostic value evaluation of exosomal crcTAOK1 in DN patients. ***P <0.001. (TIF 618 KB)

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Li, B., Sun, G., Yu, H. et al. Exosomal circTAOK1 contributes to diabetic kidney disease progression through regulating SMAD3 expression by sponging miR-520h. Int Urol Nephrol 54, 2343–2354 (2022). https://doi.org/10.1007/s11255-022-03139-y

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