Open Access

Krüppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway

  • Authors:
    • Jianguang Gong
    • Huifang Zhan
    • Yiwen Li
    • Wei Zhang
    • Juan Jin
    • Qiang He
  • View Affiliations

  • Published online on: August 9, 2019     https://doi.org/10.3892/mmr.2019.10585
  • Pages: 3240-3248
  • Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic kidney disease (DKD) is diagnosed increasingly frequently and represents a serious threat to human health. Krüppel‑like factor 4 (KLF4) has aroused attention due to its potential effect on podocytes and in ameliorating proteinuria associated with glomerulopathy. The purpose of the present study was to investigate the potential role of KLF4 in DKD. It was hypothesized that KLF4 impacts diabetic nephropathy by mediating the podocyte autophagic process. A KLF4 plasmid vector was constructed, and podocytes were transfected and incubated with DKD mice serum for in vitro experiments. A db/db spontaneous DKD mouse model was also established for in vivo study. After treatment, the level of serum creatinine (Scr), blood urea nitrogen (BUN), and 24‑h urinary protein was determined. Immunofluorescence and periodic acid‑Schiff staining, western blotting, flow cytometry and a TUNEL assay were performed to observe changes in glomerular morphology and the level of apoptosis, cytoskeleton proteins, epithelial‑mesenchymal transition (EMT) biomarkers, autophagic proteins and mTOR pathway proteins in each group. KLF4 overexpression significantly reduced the level of urinary albumin, Scr, BUN and attenuated mesangial matrix expansion, as well as mesangial cell proliferation in DKD mice. KLF4 overexpression also inhibited podocyte apoptosis and downregulated vimentin and α‑smooth muscle actin, and upregulated E‑cadherin and nephrin, both in vivo and in vitro. Moreover, the microtubule associated protein 1 light chain 3α (LC3)‑II/LC3‑I ratio and LC3‑II fluorescence was significantly increased in the vector‑KLF4 group compared to the negative control vector group both in vivo and in vitro. Finally, a decrease in the level of phosphorylated (p)‑mTOR and p‑S6K protein expression was observed following KLF4 overexpression in vitro. The present findings suggested that KLF4 plays a renoprotective role in DKD, which is associated with the activation of podocyte autophagy, and may be involved in the mTOR signaling pathway.

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October 2019
Volume 20 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
APA
Gong, J., Zhan, H., Li, Y., Zhang, W., Jin, J., & He, Q. (2019). Krüppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway. Molecular Medicine Reports, 20, 3240-3248. https://doi.org/10.3892/mmr.2019.10585
MLA
Gong, J., Zhan, H., Li, Y., Zhang, W., Jin, J., He, Q."Krüppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway". Molecular Medicine Reports 20.4 (2019): 3240-3248.
Chicago
Gong, J., Zhan, H., Li, Y., Zhang, W., Jin, J., He, Q."Krüppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway". Molecular Medicine Reports 20, no. 4 (2019): 3240-3248. https://doi.org/10.3892/mmr.2019.10585