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Article

Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway

  • Authors:
    • Di Yao
    • Suyu Wang
    • Min Wang
    • Weiping Lu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology and Metabolism, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
  • Pages: 3625-3630
    |
    Published online on: August 17, 2018
       https://doi.org/10.3892/mmr.2018.9393
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Abstract

Sodium‑glucose co‑transporter 2 (SGLT2) inhibitors are recently developed oral hypoglycemic agents, which act on renal proximal tubules by reducing the reabsorption of glucose and increasing the excretion of glucose in the urine. However, the mechanism underlying renoprotection has not been fully elucidated. Previous studies have indicated that the expression of high mobility group box 1 (HMGB1) increased in patients with kidney disease, and may result in renal damage through the activation of nuclear factor‑κB (NF‑κB) and an increase in receptor for advanced glycation end products (RAGE) expression. The aim of the present study was to evaluate the effects of the SGLT‑2 inhibitor dapagliflozin on cultured human proximal tubular epithelial cells (HK‑2). HK‑2 cells were grown under high glucose conditions for 48 h in the presence or absence of dapagliflozin. The markers of oxidative stress, inflammation and fibrillation levels were then detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. Hyperglycemia increased the mRNA expression and protein levels of malondialdehyde (MDA), superoxide dismutase (SOD), monocyte chemoattractant protein‑1 (MCP‑1), intercellular adhesion molecule‑1 (ICAM‑1), fibronectin (FN), collagenase type 1 (COL‑1), HMGB1, RAGE and NF‑κB, and the effects could be reversed by dapagliflozin in a concentration‑dependent manner. The results of the present study suggested that HMGB1 increased the expression and secretion of markers of inflammation, oxidative stress and fibrillation, including MDA, SOD, MCP‑1, ICAM‑1, FN and COL‑1, in diabetic nephropathy. However, dapagliflozin significantly reduced the levels of inflammatory markers and postponed the progression of renal injury. It was therefore suggested this may be mediated through the inhibition of HMGB1‑RAGE-NF‑κB signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Yao D, Wang S, Wang M and Lu W: Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway. Mol Med Rep 18: 3625-3630, 2018.
APA
Yao, D., Wang, S., Wang, M., & Lu, W. (2018). Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway. Molecular Medicine Reports, 18, 3625-3630. https://doi.org/10.3892/mmr.2018.9393
MLA
Yao, D., Wang, S., Wang, M., Lu, W."Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway". Molecular Medicine Reports 18.4 (2018): 3625-3630.
Chicago
Yao, D., Wang, S., Wang, M., Lu, W."Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway". Molecular Medicine Reports 18, no. 4 (2018): 3625-3630. https://doi.org/10.3892/mmr.2018.9393
Copy and paste a formatted citation
x
Spandidos Publications style
Yao D, Wang S, Wang M and Lu W: Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway. Mol Med Rep 18: 3625-3630, 2018.
APA
Yao, D., Wang, S., Wang, M., & Lu, W. (2018). Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway. Molecular Medicine Reports, 18, 3625-3630. https://doi.org/10.3892/mmr.2018.9393
MLA
Yao, D., Wang, S., Wang, M., Lu, W."Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway". Molecular Medicine Reports 18.4 (2018): 3625-3630.
Chicago
Yao, D., Wang, S., Wang, M., Lu, W."Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1‑receptor for advanced glycation end products‑nuclear factor‑κB signaling pathway". Molecular Medicine Reports 18, no. 4 (2018): 3625-3630. https://doi.org/10.3892/mmr.2018.9393
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