PMID- 31432191
OWN - NLM
STAT- MEDLINE
DCOM- 20200204
LR  - 20231014
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 20
IP  - 4
DP  - 2019 Oct
TI  - Kruppel‑like factor 4 ameliorates diabetic kidney disease by activating autophagy 
      via the mTOR pathway.
PG  - 3240-3248
LID - 10.3892/mmr.2019.10585 [doi]
AB  - Diabetic kidney disease (DKD) is diagnosed increasingly frequently and represents 
      a serious threat to human health. Kruppel‑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 alpha‑smooth muscle 
      actin, and upregulated E‑cadherin and nephrin, both in vivo and in vitro. 
      Moreover, the microtubule associated protein 1 light chain 3alpha (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.
FAU - Gong, Jianguang
AU  - Gong J
AD  - Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 
      Zhejiang 310014, P.R. China.
FAU - Zhan, Huifang
AU  - Zhan H
AD  - Department of Emergency, Zhejiang University Hospital, Hangzhou, Zhejiang 310058, 
      P.R. China.
FAU - Li, Yiwen
AU  - Li Y
AD  - Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 
      Zhejiang 310014, P.R. China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 
      Zhejiang 310014, P.R. China.
FAU - Jin, Juan
AU  - Jin J
AD  - Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 
      Zhejiang 310014, P.R. China.
FAU - He, Qiang
AU  - He Q
AD  - Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 
      Zhejiang 310014, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190809
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (KLF4 protein, human)
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Autophagic Cell Death
MH  - Cell Line, Transformed
MH  - Diabetic Nephropathies/genetics/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation
MH  - Glomerular Mesangium/*metabolism/pathology
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/*biosynthesis/genetics
MH  - Male
MH  - Mice
MH  - Podocytes/*metabolism/pathology
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC6755248
EDAT- 2019/08/23 06:00
MHDA- 2020/02/06 06:00
PMCR- 2019/08/09
CRDT- 2019/08/22 06:00
PHST- 2019/02/12 00:00 [received]
PHST- 2019/07/05 00:00 [accepted]
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/08/22 06:00 [entrez]
PHST- 2019/08/09 00:00 [pmc-release]
AID - mmr-20-04-3240 [pii]
AID - 10.3892/mmr.2019.10585 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Oct;20(4):3240-3248. doi: 10.3892/mmr.2019.10585. Epub 2019 Aug 
      9.