scholarly journals Triptolide Attenuates Renal Tubular Epithelial-mesenchymal Transition Via the MiR-188-5p-mediated PI3K/AKT Pathway in Diabetic Kidney Disease

2018 ◽  
Vol 14 (11) ◽  
pp. 1545-1557 ◽  
Author(s):  
Mei Xue ◽  
Ying Cheng ◽  
Fei Han ◽  
Yunpeng Chang ◽  
Yang Yang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Epithelial Mesenchymal Transition ◽  
Akt Pathway ◽  
Diabetic Kidney ◽  
Mesenchymal Transition ◽  
Renal Tubular

miR302a-3p May Modulate Renal Epithelial-Mesenchymal Transition in Diabetic Kidney Disease by Targeting ZEB1

Nephron ◽  
2017 ◽  
Vol 138 (3) ◽  
pp. 231-242 ◽  
Author(s):  
Wen-bin Tang ◽  
Linfeng Zheng ◽  
Renheng Yan ◽  
Jiayi Yang ◽  
Jianping Ning ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Epithelial Mesenchymal Transition ◽  
Diabetic Kidney ◽  
Mesenchymal Transition

scholarly journals Klotho prevents epithelial–mesenchymal transition through Egr-1 downregulation in diabetic kidney disease

2021 ◽  
Vol 9 (1) ◽  
pp. e002038
Author(s):  
Yang Li ◽  
Meng Xue ◽  
Fang Hu ◽  
Yijie Jia ◽  
Zongji Zheng ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Signaling Pathway ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Diabetic Kidney ◽  
Mesenchymal Transition ◽  
Hk2 Cells ◽  
Tgf Β1

IntroductionAs a key event leading to tubulointerstitial fibrosis in diabetic kidney disease (DKD), epithelial–mesenchymal transition (EMT) has drawn increasing attention from researchers. The antiaging protein Klotho attenuates renal fibrosis in part by inhibiting ERK1/2 signaling in DKD. Early growth response factor 1 (Egr-1), which is activated mainly by ERK1/2, has been shown to play an important role in EMT. However, whether Klotho prevents EMT by inhibiting ERK1/2-dependent Egr-1 expression in DKD is unclear.The aim of this study was to investigate whether Klotho prevents EMT through Egr-1 downregulation by inhibiting the ERK1/2 signaling pathway in DKD.Research design and methodsMale C57BL/6J mice fed an high-fat diet for 4 weeks received 120 mg/kg streptozotocin (STZ), which was injected intraperitoneally. Klotho and Egr-1 expression was detected in the renal cortices of these mice on their sacrifice at 6 and 12 weeks after STZ treatment. In In vitro studies, we incubated HK2 cells under high-glucose (HG) or transforming growth factor-β1 (TGF-β1) conditions to mimic DKD. We then transfected the cells with an Klotho-containing plasmid, Klotho small interfering RNA.ResultsKlotho expression was significantly decreased in the renal cortices of mice with diabetes mellitus (DM) compared with the renal cortices of control mice at 6 weeks after treatment and even more significantly decreased at 12 weeks. In contrast, Egr-1 expression was significantly increased in mice with DM compared with control mice only at 12 weeks. We also found that Klotho overexpression downregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Conversely, Klotho silencing upregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Moreover, the effects of si-Klotho were abolished by the ERK1/2 inhibitor PD98059.ConclusionsKlotho prevents EMT during DKD progression, an effect that has been partially attributed to Egr-1 downregulation mediated by ERK1/2 signaling pathway inhibition.

Klotho Prevents Epithelial-Mesenchymal Transition through Egr-1 Down-Regulation in Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 509-P
Author(s):  
YANG LI ◽  
MENG XUE ◽  
FANG HU ◽  
YIJIE JIA ◽  
YAN-LIN YANG ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Epithelial Mesenchymal Transition ◽  
Down Regulation ◽  
Diabetic Kidney ◽  
Mesenchymal Transition

scholarly journals TRIM18-Regulated STAT3 Signaling Pathway via PTP1B Promotes Renal Epithelial–Mesenchymal Transition, Inflammation, and Fibrosis in Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Chen ◽  
Chan Gao ◽  
Ming Wang ◽  
Xiao Fei ◽  
Ning Zhao
Keyword(s):  
Kidney Disease ◽  
Signaling Pathway ◽  
Diabetic Kidney Disease ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Tissue Growth ◽  
Diabetic Kidney ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Diabetic kidney disease (DKD) has become a key cause of end-stage renal disease worldwide. Inflammation and fibrosis have been shown to play important roles in the pathogenesis of DKD. MID1, also known as TRIM18, is an E3 ubiquitin ligase of the tripartite motif (TRIM) subfamily of RING-containing proteins and increased in renal tubule in patients with DKD. However, the function and molecular mechanism of TRIM18 in DKD remain unexplored. Herein we report that TRIM18 expression levels were increased in patients with DKD. An animal study confirms that TRIM18 is involved in kidney injury and fibrosis in diabetic mice. TRIM18 knockdown inhibits high glucose (HG)-induced epithelial–mesenchymal transition (EMT), inflammation, and fibrosis of HK-2 cells. This is accompanied by decreased levels of tumor necrosis factor alpha, interleukin-6, hydroxyproline (Hyp), connective tissue growth factor, and α-smooth muscle actin. Additionally, TRIM18 knockdown inhibits HG-induced increase in the phosphorylated-/total signal transducer and activator of transcription (STAT3). Treatment with niclosamide (STAT3 inhibitor) or protein tyrosine phosphatase-1B (PTP1B) overexpression blocked the TRIM18 induced EMT, inflammation and fibrosis. Co-immunoprecipitation and Western blot assays showed that TRIM18 promoted the ubiquitination of PTP1B. These findings highlight the importance of the TRIM18/PTP1B/STAT3 signaling pathway in DKD and can help in the development of new therapeutics for DKD treatment.

scholarly journals PTEN-induced partial epithelial-mesenchymal transition drives diabetic kidney disease

2019 ◽  
Vol 129 (3) ◽  
pp. 1129-1151 ◽  
Author(s):  
Yajuan Li ◽  
Qingsong Hu ◽  
Chunlai Li ◽  
Ke Liang ◽  
Yu Xiang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Epithelial Mesenchymal Transition ◽  
Diabetic Kidney ◽  
Mesenchymal Transition

scholarly journals 20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Tong Zhou ◽  
Lin Sun ◽  
Shuo Yang ◽  
You Lv ◽  
Yue Cao ◽  
...  
Keyword(s):  
Treatment Group ◽  
Kidney Disease ◽  
Cell Apoptosis ◽  
Diabetic Kidney Disease ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Renal Tubular Cell ◽  
Ginsenoside Rg3 ◽  
Diabetic Kidney ◽  
Renal Tubular

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.

scholarly journals Effects of ZnT8 on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis in diabetic kidney disease

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Xiuli Zhang ◽  
Tingwen Guan ◽  
Boxuan Yang ◽  
Harvest F. Gu ◽  
Zhihong Chi
Keyword(s):  
Kidney Disease ◽  
Pancreatic Beta Cells ◽  
Diabetic Kidney Disease ◽  
Epithelial To Mesenchymal Transition ◽  
Gene Transfection ◽  
Tubulointerstitial Fibrosis ◽  
Inflammatory Factors ◽  
Diabetic Kidney ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Zinc transporter 8 (ZnT8) transports zinc ions for crystallization and storage of insulin in pancreatic beta-cells and ZnT8 dysfunction is involved in pathogenesis of diabetes. The current study aimed to investigate whether ZnT8 has effects in pathophysiology of diabetic kidney disease (DKD) by using animal models for diabetes, including STZ-induced diabetic, db/db, ZnT8-KO, ZnT8-KO-STZ and ZnT8-KO-db/db mice. Results demonstrated that urine albumin to creatinine ratio and epithelial-to-mesenchymal transition (EMT) were increased in kidneys of ZnT8-KO-STZ and ZnT8-KO-db/db mice compared with C57BL/6 J and ZnT8-KO mice, while serum TGF-β1, IL-6, and TNF-α levels were elevated in parallel. In kidneys of mice intercrossed between ZnT8-KO and STZ-induced diabetic or db/db mice, these three inflammatory factors, ACR and EMT were also found to be increased compared with C57BL/6J, db/db and ZnT8-KO mice. Furthermore, ZnT8 up-regulation by hZnT8-EGFP reduced the levels of high glucose (HG)-induced EMT and inflammatory factors in normal rat kidney tubular epithelial cell (NRK-52E cells). Expression of phosphorylated Smad2/Smad3 was up-regulated after HG stimulation and further enhanced by ZnT8 siRNA but down-regulated after hZnT8-EGFP gene transfection. The current study thus provides the first evidence that ZnT8 protects against EMT-tubulointerstitial fibrosis though the restrain of TGF-β1/Smads signaling activation in DKD.

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