scholarly journals CXCL6 Promotes Renal Interstitial Fibrosis in Diabetic Nephropathy by Activating JAK/STAT3 Signaling Pathway

2019 ◽  
Vol 10 ◽  
Author(s):  
Meng-Yao Sun ◽  
Su-Juan Wang ◽  
Xiao-Qin Li ◽  
Yu-Li Shen ◽  
Jian-Rao Lu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Renal Interstitial Fibrosis ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy

2019 ◽  
Author(s):  
Liming Guo ◽  
Kuibi Tan ◽  
Qun Luo ◽  
Xu Bai
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Rat Model ◽  
Interstitial Fibrosis ◽  
Mtor Signaling ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Mtor Signaling Pathway ◽  
Renal Interstitial Fibrosis ◽  
Gene Assay

Diabetic nephropathy (DN) is the most common complication of diabetes and is prone to kidney failure. Dihydromyricetin (DHM) has been reported to have a variety of pharmacological activities. This study aims to explore the effect of DHM on DN and the underlying molecular mechanism. An in vivo DN rat model was established. The degree of renal interstitial fibrosis (RIF) was detected by hematoxylin-eosin (HE) staining, Masson's trichrome staining, and immunohistochemistry (IHC). In vitro, NRK-52E cells were divided into four groups: normal glucose (NG), high glucose (HG), HG+DHM, and HG+rapamycin (autophagy inhibitor). The levels of autophagy- and fibrosis-related proteins were analyzed by western blotting. The expression of miR-155-5p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) and their relationship were assessed by quantitative reverse transcription (qRT)-PCR and dual luciferase reporter gene assay. Our results showed that RIF was increased in DN rat model and in HG-induced NRK-52E cells. DHM treatment attenuated the increased RIF and also increased autophagy. MiR-155-5p expression was increased, while PTEN expression was decreased in DN rat and cell model, and DHM reversed both effects. Dual luciferase assay showed that PTEN was the target gene of miR-155-5p. DHM inhibited HG-induced fibrosis and promoted autophagy by inhibiting miR-155-5p expression in NRK-52E cells. In addition, DHM promoted autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, DHM promotes autophagy and attenuates RIF by regulating the miR-155-5p/PTEN signaling and PI3K/AKT/mTOR signaling pathway in DN.

scholarly journals Renoprotective Effect of the Recombinant Anti-IL-6R Fusion Proteins by Inhibiting JAK2/STAT3 Signaling Pathway in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Nanwen Zhang ◽  
Qingmei Zheng ◽  
Yaduan Wang ◽  
Juan Lin ◽  
He Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Interleukin 6 ◽  
Fusion Proteins ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Stat3 Pathway ◽  
Renoprotective Effect ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Diabetic nephropathy the main reason for end stage renal disease is a common microvascular complication in patients with type 1 and type 2 diabetes. The interleukin-6 (IL-6), acting as a pleiotropic cytokine, play key roles in main autoimmune disorders. The recombinant anti-IL-6R fusion proteins (VHH-0031) constructed and obtained in our lab is a dual target-directed single domain-based fusion protein against the interleukin-6 receptor. This study aims to explore the renoprotective effect of VHH-0031 in diabetic nephropathy. VHH-0031 treatment alleviated renal inflammation, morphologic injury and renal insufficiency in both Goto-Kakizaki rats and STZ-induced Sprague Dawley rats. These renoprotective effects of VHH-0031 are associated with alleviating inflammation and suppression of the JAK2/STAT3 signaling pathway. The mesangial cells treated with VHH-0031 exhibited anti-proliferation, anti-inflammation and inactivation of JAK2/STAT3 pathway under high glucose condition. In conclusion, this study demonstrates that VHH-0031 exhibited a potent protective effect in kidney of diabetic rats and its mechanism may be concerned with the inhibition of the IL-6R/JAK2/STAT3 pathway of glomerular mesangial cells.

scholarly journals Gliquidone Alleviates Diabetic Nephropathy by Inhibiting Notch/Snail Signaling Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2085-2097 ◽  
Author(s):  
Hengyu Tian ◽  
Junbo Yang ◽  
Zhuochao Xie ◽  
Jialin  Liu
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Body Weight ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
High Dose ◽  
Renal Interstitial Fibrosis ◽  
Biochemical Analyzer ◽  
Automatic Biochemical Analyzer

Background/Aims: Diabetic nephropathy is a common complication of diabetes. This study explored the renal protective effect and possible mechanism of gliquidone in mice with diabetic nephropathy. Methods: Animal model of diabetic nephropathy was established in KKAy mice. The renal protective effect of gliquidone was studied by evaluating the kidney function through measures of urinary protein, blood urea nitrogen (BUN), serum creatinine (Scr) and serum triglyceride (TG) that were performed using an automatic biochemical analyzer. The levels of oxidative stress indicators, such as nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA), were evaluated in renal tissue homogenates using the automatic biochemical analyzer. The inhibitory effect of gliquidone on renal interstitial fibrosis and its association with Notch / Snail1 signaling pathway in diabetic nephropathy was investigated using molecular biological techniques. Results: It was found that low-, medium- and high-dose gliquidone improved the mice’s general health condition, such as mental status, fur condition, eating, and drinking. Gliquidone reduced the body weight and the kidney weight /body weight ratio of mice. Gliquidone improved the kidney function, indicated by reductions in urinary protein, blood urea nitrogen, and serum creatinine and triglyceride. Gliquidone treatment increased levels of nitric oxide and superoxide dismutase, but decreased level of malondialdehyde. The expression of Jagged1/Notch1/hes1/Snail1/α-SMA decreased, while the expression of E-cadherin increased in gliquidone-treated kidneys. High dose gliquidone showed the best effect, one that was similar to that of the positive control drug irbesartan. Conclusion: Taken together, our results suggested that gliquidone can ameliorate the diabetic symptoms of diabetic nephropathy through inhibiting Notch / Snail1 signaling pathway, improving anti -oxidative response and delaying renal interstitial fibrosis. The efficacy of gliquidone is dose-dependent.

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