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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 / Copyright

    Affiliations: Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Department of Emergency, Zhejiang University Hospital, Hangzhou, Zhejiang 310058, P.R. China
    Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3240-3248
    |
    Published online on: August 9, 2019
       https://doi.org/10.3892/mmr.2019.10585
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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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1 

Cunningham A, Benediktsson H, Muruve DA, Hildebrand AM and Ravani P: Trends in biopsy-based diagnosis of kidney disease: A population study. Can J Kidney Health Dis. 5:20543581187996902018. View Article : Google Scholar : PubMed/NCBI

2 

Huang YM, Xu D, Long J, Shi Y, Zhang L, Wang H, Levin A and Zhao MH: The spectrum of chronic kidney disease in China: A national study based on hospitalized patients from 2010 to 2015. Nephrology (Carlton). 24:725–736. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Pontrelli P, Oranger A, Barozzino M, Divella C, Conserva F, Fiore MG, Rossi R, Papale M, Castellano G, Simone S, et al: Deregulation of autophagy under hyperglycemic conditions is dependent on increased lysine 63 ubiquitination: A candidate mechanism in the progression of diabetic nephropathy. J Mol Med (Berl). 96:645–659. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Dai H, Liu Q and Liu B: Research progress on mechanism of podocyte depletion in diabetic nephropathy. J Diabetes Res. 2017:26152862017. View Article : Google Scholar : PubMed/NCBI

5 

Yamaguchi Y, Iwano M, Suzuki D, Nakatani K, Kimura K, Harada K, Kubo A, Akai Y, Toyoda M, Kanauchi M, et al: Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy. Am J Kidney Dis. 54:653–664. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Ghaleb AM and Yang VW: Krüppel-like factor 4 (KLF4): What we currently know. Gene. 611:27–37. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Yoshida T, Yamashita M, Iwai M and Hayashi M: Endothelial krüppel-like factor 4 mediates the protective effect of statins against ischemic AKI. J Am Soc Nephrol. 27:1379–1388. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Hayashi K, Sasamura H, Nakamura M, Azegami T, Oguchi H, Sakamaki Y and Itoh H: KLF4-dependent epigenetic remodeling modulates podocyte phenotypes and attenuates proteinuria. J Clin Invest. 124:2523–2537. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Gong J, Jin J, Zhao L, Li Y, Li Y and He Q: Tripterygium glycoside protects against puromycin amino nucleoside-induced podocyte injury by upregulating autophagy. Int J Mol Med. 42:115–122. 2018.PubMed/NCBI

10 

Tesch GH and Lim AK: Recent insights into diabetic renal injury from the db/db mouse model of type 2 diabetic nephropathy. Am J Physiol Renal Physiol. 300:F301–F3010. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Mallipattu SK, Guo Y, Revelo MP, Roa-Peña L, Miller T, Ling J, Shankland SJ, Bialkowska AB, Ly V, Estrada C, et al: Krüppel-Like factor 15 mediates glucocorticoid-induced restoration of podocyte differentiation markers. J Am Soc Nephrol. 28:166–184. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Mallipattu SK, Estrada CC and He JC: The critical role of Krüppel-like factors in kidney disease. Am J Physiol Renal Physiol. 312:F259–F265. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Vogelmann SU, Nelson WJ, Myers BD and Lemley KV: Urinary excretion of viable podocytes in health and renal disease. Am J Physiol Renal Physiol. 285:F40–F48. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Loeffler I and Wolf G: Epithelial-to-mesenchymal transition in diabetic nephropathy: Fact or fiction. Cells. 4:631–652. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Lin L, Han Q, Xiong Y, Li T, Liu Z, Xu H, Wu Y, Wang N and Liu X: Krüpple-like-factor 4 attenuates lung fibrosis via inhibiting epithelial-mesenchymal transition. Sci Rep. 7:158472017. View Article : Google Scholar : PubMed/NCBI

16 

Chen WC, Lin HH and Tang MJ: Matrix-stiffness-regulated inverse expression of Krüppel-like factor 5 and Krüppel-like factor 4 in the pathogenesis of renal fibrosis. Am J Pathol. 185:2468–2481. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Pinho AV, Rooman I and Real FX: p53-dependent regulation of growth, epithelial-mesenchymal transition and stemness in normal pancreatic epithelial cells. Cell Cycle. 10:1312–1321. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Dong P, Kaneuchi M, Watari H, Hamada J, Sudo S, Ju J and Sakuragi N: MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer. 10:992011. View Article : Google Scholar : PubMed/NCBI

19 

Wada J and Makino H: Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond). 124:139–152. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Li Z, Jia Y, Han S, Wang X, Han F, Zhang J, Zhang W, Guan H and Hu D: Klf4 alleviates lipopolysaccharide-induced inflammation by inducing expression of MCP-1 induced protein 1 to deubiquitinate TRAF6. Cell Physiol Biochem. 47:2278–2290. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Jin J, Wu D, Zhao L Zou W, Shen W, Tu Q and He Q: Effect of autophagy and stromal interaction molecule 1 on podocyte epithelial-mesenchymal transition in diabetic nephropathy. Int J Clin Exp Pathol. 5:2450–2459. 2018.

22 

Lenoir O, Jasiek M, Hénique C, Guyonnet L, Hartleben B, Bork T, Chipont A, Flosseau K, Bensaada I, Schmitt A, et al: Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis. Autophagy. 11:1130–1145. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Tagawa A, Yasuda M, Kume S, Yamahara K, Nakazawa J, Chin-Kanasaki M, Araki H, Araki S, Koya D, Asanuma K, et al: Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy. Diabetes. 65:755–767. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Riz I, Hawley TS and Hawley RG: KLF4-SQSTM1/p62-associated prosurvival autophagy contributes to carfilzomib resistance in multiple myeloma models. Oncotarget. 6:14814–14831. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Liu C, DeRoo EP, Stecyk C, Wolsey M, Szuchnicki M and Hagos EG: Impaired autophagy in mouse embryonic fibroblasts null for Krüppel-like Factor 4 promotes DNA damage and increases apoptosis upon serum starvation. Mol Cancer. 14:1012015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Gong J, Zhan H, Li Y, Zhang W, Jin J and He Q: Krüppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway. Mol Med Rep 20: 3240-3248, 2019.
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
Copy and paste a formatted citation
x
Spandidos Publications style
Gong J, Zhan H, Li Y, Zhang W, Jin J and He Q: Krüppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway. Mol Med Rep 20: 3240-3248, 2019.
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
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