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CircTLK1 Downregulation Attenuates High Glucose-Induced Human Mesangial Cell Injury by Blocking the AKT/NF-κB Pathway Through Sponging miR-126-5p/miR-204-5p

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Abstract

Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Circular RNA hsa_circ_0004442 (circTLK1) accelerates the progression of renal cell carcinoma. However, the role of circTLK1 in DN pathogenesis is indistinct. The expression of circTLK1, microRNA-126-5p (miR-126-5p), and microRNA-204-5p (miR-204-5p) was tested by quantitative real-time polymerase chain reaction. The levels of interleukin-6 and interleukin-1β were measured by enzyme-linked immunosorbent assay. The levels of reactive oxygen species and malondialdehyde and the activity of superoxide dismutase were determined with corresponding kits. Several protein levels were evaluated with western blotting. The relationship between circTLK1 and miR-126-5p/miR-204-5p was verified by dual-luciferase reporter assay. CircTLK1 was highly expressed in DN patient’s serum and high-glucose (HG)-treated human mesangial cells. Functionally, circTLK1 inhibition reduced HG-induced inflammation, oxidative stress, and ECM accumulation in human mesangial cells. CircTLK1 was verified as a sponge for miR-126-5p and miR-204-5p, which were downregulated in DN patient’s serum and HG-treated human mesangial cells. Both miR-126-5p and miR-204-5p upregulation decreased inflammation, oxidative stress, and ECM accumulation in HG-treated human mesangial cells and circTLK1 silencing-mediated influence on HG-induced human mesangial cell injury was overturned by miR-126-5p or miR-204-5p inhibition. Moreover, circTLK1 knockdown blocked the AKT/NF-κB pathway by sponging miR-126-5p/miR-204-5p. CircTLK1 downregulation alleviated HG-induced inflammation, oxidative stress, and ECM accumulation through blocking the AKT/NF-κB pathway via sponging miR-126-5p/miR-204-5p, providing a new mechanism to comprehend the pathogenesis of DN.

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Authors and Affiliations

  1. Department of General Medicine, Weifang People’s Hospital, Weifang, 261041, Shandong, China

    Binghua Qiu

  2. Department of Science and Education, People’s Hospital of Gaoxin Weifang, Weifang, 261041, Shandong, China

    Xin Qi

  3. Department of Gastroenterology, the First Hospital of Zibo City, No. 4, Emeishan East Road, Boshan District, Zibo, 255200, Shandong, China

    Juan Wang

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  1. Binghua Qiu
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  2. Xin Qi
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  3. Juan Wang
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Correspondence to Juan Wang.

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Qiu, B., Qi, X. & Wang, J. CircTLK1 Downregulation Attenuates High Glucose-Induced Human Mesangial Cell Injury by Blocking the AKT/NF-κB Pathway Through Sponging miR-126-5p/miR-204-5p. Biochem Genet 60, 1471–1487 (2022). https://doi.org/10.1007/s10528-021-10146-8

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