| First Author | Gong J | Year | 2019 |
| Journal | Mol Med Rep | Volume | 20 |
| Issue | 4 | Pages | 3240-3248 |
| PubMed ID | 31432191 | Mgi Jnum | J:290470 |
| Mgi Id | MGI:6435389 | Doi | 10.3892/mmr.2019.10585 |
| Citation | Gong J, et al. (2019) Kruppellike factor 4 ameliorates diabetic kidney disease by activating autophagy via the mTOR pathway. Mol Med Rep 20(4):3240-3248 |
| abstractText | Diabetic kidney disease (DKD) is diagnosed increasingly frequently and represents a serious threat to human health. Kruppellike 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 24h urinary protein was determined. Immunofluorescence and periodic acidSchiff staining, western blotting, flow cytometry and a TUNEL assay were performed to observe changes in glomerular morphology and the level of apoptosis, cytoskeleton proteins, epithelialmesenchymal 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 alphasmooth muscle actin, and upregulated Ecadherin and nephrin, both in vivo and in vitro. Moreover, the microtubule associated protein 1 light chain 3alpha (LC3)II/LC3I ratio and LC3II fluorescence was significantly increased in the vectorKLF4 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 pS6K 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. |
