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CircTLK1 Downregulation Attenuates High Glucose-Induced Human Mesangial Cell Injury by Blocking the AKT/NF-κB Pathway

Binghua Qiu1, Xin Qi2, Juan Wang3

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

Biochemical Genetics
|November 3, 2021
PubMed

Insights

Circular RNA hsa_circ_0004442 (circTLK1) promotes diabetic nephropathy by increasing inflammation and oxidative stress. Inhibiting circTLK1 may offer a therapeutic strategy for diabetic kidney disease.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nephrology

Background:

  • Diabetic nephropathy (DN) is a leading cause of end-stage renal disease.
  • Circular RNAs (circRNAs) are implicated in various diseases, but the role of circTLK1 in DN is unclear.
  • circTLK1 is known to promote renal cell carcinoma progression.

Purpose of the Study:

  • To investigate the role and mechanism of circTLK1 in the pathogenesis of diabetic nephropathy.
  • To explore the relationship between circTLK1, microRNAs (miRNAs), and the AKT/NF-κB pathway in DN.
  • To assess the potential of circTLK1 as a therapeutic target for DN.

Main Methods:

  • Quantitative real-time PCR to measure circTLK1, miR-126-5p, and miR-204-5p expression.
  • ELISA for inflammatory cytokines (IL-6, IL-1β), and kits for oxidative stress markers (ROS, MDA, SOD).
  • Western blotting for protein levels, dual-luciferase reporter assay for circRNA-miRNA interaction, and cell culture models.

Main Results:

  • CircTLK1 was upregulated in DN patients and high-glucose treated mesangial cells.
  • CircTLK1 inhibition reduced inflammation, oxidative stress, and extracellular matrix (ECM) accumulation.
  • CircTLK1 acts as a sponge for miR-126-5p and miR-204-5p, and its knockdown inhibits the AKT/NF-κB pathway.

Conclusions:

  • CircTLK1 exacerbates DN by promoting inflammation, oxidative stress, and ECM accumulation.
  • CircTLK1 exerts its effects by sponging miR-126-5p and miR-204-5p, thereby activating the AKT/NF-κB pathway.
  • CircTLK1 downregulation offers a potential therapeutic strategy for diabetic nephropathy.

Keywords:
AKT/NF-κBDNHGcircTLK1miR-126-5pmiR-204-5p

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