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.

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 Effects of Qingshen Granules on the Oxidative Stress-NF/kB Signal Pathway in Unilateral Ureteral Obstruction Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Hua Jin ◽  
Yiping Wang ◽  
Dong Wang ◽  
Lei Zhang
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Signal Pathway ◽  
Unilateral Ureteral Obstruction ◽  
High Dose ◽  
Renal Tubules ◽  
Renal Interstitial Fibrosis ◽  
Mesenchymal Transition

Background. The activation of NF-kappa B (NF/kB) signaling pathway plays an important role in the process of epithelial-mesenchymal transition (EMT) and renal interstitial fibrosis (RIF) in renal tubules. The process of oxidative stress reaction in kidney is via excessive reactive oxygen species (ROS) production to activate NF/kB signaling pathway. Qingshen Granule (QSG) is an effective Chinese formula utilized to treat chronic renal failure. Previous studies confirmed that QSG could inhibit RIF in unilateral ureteral obstruction (UUO) rats. In this study, we used UUO rats to investigate the effects of QSG on oxidative stress and the activation of NF/kB signaling. Seventy male Sprague-Dawley (SD) rats were randomly divided into a sham group, UUO model group, Qingshen Granules (QSG) high-dose, medium-dose, and low-dose groups, PDTC group, and candesartan group (10 rats in each group). Our study demonstrated that oxidative stress-NF/kB signal pathway contributed to the formation of UUO renal interstitial fibrosis. QSG may protect against RIF by inhibiting the oxidative stress-NF/kB signal pathway, reducing inflammation, and improving renal tubular EMT.

Fucoidans from Cucumaria frondosa ameliorates renal interstitial fibrosis via inhibition of PI3K/Akt/NF-κB signaling pathway

2022 ◽  
Author(s):  
Zhuo-yue Song ◽  
Mengru Zhu ◽  
Jun Wu ◽  
Tian Yu ◽  
Yao Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Protein Kinase B ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Renal Interstitial Fibrosis ◽  
Cucumaria Frondosa

The effects of Cucumaria frondosa polysaccharides (CFP) on renal interstitial fibrosis via regulating phosphatidylinositol-3-hydroxykinase/protein kinase-B/Nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated in vivo and in vitro in this research. A...

scholarly journals Characterization of fluoroquinolone-induced Achilles tendon toxicity in rats: comparison of toxicities of 10 fluoroquinolones and effects of anti-inflammatory compounds.

1997 ◽  
Vol 41 (11) ◽  
pp. 2389-2393 ◽  
Author(s):  
Y Kashida ◽  
M Kato
Keyword(s):  
Nitric Oxide ◽  
Body Weight ◽  
Methyl Ester ◽  
Achilles Tendon ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
High Dose ◽  
Juvenile Rats ◽  
Anti Inflammatory

Fluoroquinolone antibacterial agents have been reported to induce tendon lesions in juvenile rats. In the present study, we characterized fluoroquinolone-induced Achilles tendon lesions by comparing the effects of 10 fluoroquinolones and examining the potential of one of these antimicrobial agents, pefloxacin, to induce tendon lesions when coadministered with one of nine anti-inflammatory compounds. Among the 10 fluoroquinolones tested, fleroxacin and pefloxacin were the most toxic, inducing lesions at a dose of 100 mg/kg of body weight or more, while lomefloxacin, levofloxacin, and ofloxacin or sparfloxacin and enoxacin induced lesions at 300 mg/kg or more and 900 mg/kg, respectively. In contrast, norfloxacin, ciprofloxacin, and tosufloxacin had no effect even at the high dose of 900 mg/kg. The severity of the Achilles tendon lesions appeared to correlate with the structure of the substituent at the seventh position. Furthermore, pefloxacin-induced tendon lesions were inhibited by coadministration with dexamethasone and N-nitro-L-arginine methyl ester. Phenidone (1-phenyl-3-pyrazolidinone) and 2-(12-hydroxydodeca-5,10-diynyl)3,5,6-trimethyl-1,4-benzoqui none (AA861) also decreased the incidence of tendon lesions. In contrast, catalase, dimethyl sulfoxide, indomethacin, pyrilamine, and cimetidine did not modify these tendon lesions. These results suggest that nitric oxide and 5-lipoxigenase products partly mediate fluoroquinolone-induced tendon lesions.

scholarly journals Silencing of long noncoding RNA XIST protects against renal interstitial fibrosis in diabetic nephropathy via microRNA-93-5p-mediated inhibition of CDKN1A

2019 ◽  
Vol 317 (5) ◽  
pp. F1350-F1358 ◽  
Author(s):  
Jindou Yang ◽  
Yan Shen ◽  
Xia Yang ◽  
Yanjun Long ◽  
Shuang Chen ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanism ◽  
High Glucose ◽  
Noncoding Rna ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Kidney Tissue ◽  
Luciferase Reporter ◽  
Renal Interstitial Fibrosis ◽  
Endogenous Expression

Long noncoding RNAs (lncRNAs) have been reported to play an important role in diabetic nephropathy (DN). However, the molecular mechanism involved in this process remains poorly understood. Thus, the present study aimed to explore the function and molecular mechanism of dysregulated lncRNA X-inactive specific transcript (XIST) in DN. DN mouse models were established by streptozotocin treatment, and human renal tubular epithelial HK-2 cells were exposed to high glucose to produce an in vitro model. XIST was highly expressed in renal tissues of patients with DN, mice with DN, and high glucose-exposed HK-2 cells. To identify the interaction among XIST, miR-93-5p, and cyclin-dependent kinase inhibitor 1A (CDKN1A) and to analyze the functional significance of their interaction in renal interstitial fibrosis, we altered endogenous expression of XIST and miR-93-5p and CDKN1A. Dual-luciferase reporter assay results suggested that XIST was highly expressed in the kidney tissue of DN mice and high glucose-exposed HK-2 cells. XIST was identified to be a lncRNA that could bind to miR-93-5p, and CDKN1A was a target of miR-93-5p. Downregulated expression of XIST led to an increase in miR-93-5p expression, thereby decreasing CDKN1A and suppressing renal interstitial fibrosis in DN. Consistently, XIST knockdown reduced the expression of fibrosis markers (fibronectin, collagen type IV, and transforming growth factor-β1). Restoration of CDKN1A or decreasing miR-93-5p yielded a reversed effect on renal interstitial fibrosis. In conclusion, our study demonstrated that silenced XIST inducing miR-93-5p-dependent CDKN1A inhibition was beneficial for preventing renal interstitial fibrosis in DN, which may provide a future strategy to prevent the progression of DN.

scholarly journals GSTA3 regulates TGF-β1-induced renal interstitial fibrosis in NRK-52E cells as a component of the PI3K–Keap1/Nrf2 pathway

2019 ◽  
Vol 47 (11) ◽  
pp. 5787-5801
Author(s):  
Yun Xiao ◽  
Zhiwei Zhang ◽  
Yingyu Fu ◽  
Huizhi Shan ◽  
Sini Cui ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Mapk Pathway ◽  
Mrna Levels ◽  
Renal Interstitial Fibrosis ◽  
Nrf2 Pathway ◽  
Nrf2 Signaling Pathway ◽  
Nrf2 Expression ◽  
Tgf Β1

Objective To evaluate the effect of GSTA3 within the PI3K–Keap1/Nrf2 pathway in renal interstitial fibrosis (RIF). Methods An in vitro RIF model with TGF-β1 stimulation in NRK-52E cells was established to identify potential signaling pathways that modulate GSTA3. Changes in GSTA3 expression were observed in the RIF model after silencing or enhancing Nrf2 expression. Changes in GSTA3, Keap1, and Nrf2 expression were detected after blocking the upstream of the Keap1/Nrf2 signaling pathway (including MAPK and PI3K/Akt). The effect of Nrf2 on GSTA3 expression was evaluated by overexpressing Nrf2. Results Protein and mRNA levels of GSTA3, FN, Nrf2, and Keap1 were significantly increased after TGF-β1 stimulation. GSTA3 was also upregulated following overexpression of Nrf2. TGF-β1 activated the PI3K/Akt signaling pathway, leading to RIF. After blocking this pathway, the production of superoxide dismutase, reactive oxygen species, and fibronectin were reduced. The MAPK pathway was not involved in the development of RIF via regulating GSTA3 expression. Conclusions The PI3K–KEAP1/Nrf2–GSTA3 signaling pathway is a possible mechanism of resisting external stimulation of renal fibrosis factors, regulating oxidative stress, and preventing RIF.

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