Gliquidone Alleviates Diabetic Nephropathy by Inhibiting Notch/Snail Signaling Pathway

Tian, Hengyu; Yang, Junbo; Xie, Zhuochao; Liu, Jialin

doi:10.1159/000495827

Cited by 29 publications

(19 citation statements)

References 30 publications

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“…Here, we found that LWDH showed a significant role in reducing serum fasting blood glucose, creatinine, blood urine nitrogen, urine volume, urinary ALB, urinary creatinine, and the renal index levels in DNOP rats. In addition, morphological observation of kidney tissue can effectively reveal the pathological condition of DN, including glomerular hypertrophy, GBM thickening, infiltration It is established that EMT is a common and complicated pathological process observed in DN rats [24]. In the present study, LWDH treatment significantly decreased the expression of α-SMA and Vimentin levels and increased the level E-cadherin protein of rats after 12 weeks compared with the DNOP group.…”

Section: Discussionsupporting

confidence: 51%

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Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis

et al. 2020

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The effects of Liuwei Dihuang Pill (LWDH) on diabetic nephropathy-related osteoporosis (DNOP) are unclear. This study aimed to evaluate the effects of LWDH on KDM7A and Wnt/β-catenin signaling pathway in DNOP rats and the high glucose-induced MC3T3-E1 cells. A DNOP model was prepared by streptozotocin in 9-week old male Sprague-Dawley(SD) rats to evaluate the effects of LWDH. The cell viability and differentiation capacity of high glucose-induced MC3T3-E1 cells were determined by CCK-8 assay, Alizarin Red staining, and alkaline phosphatase (ALP) staining, respectively. Furthermore, the expressions of KDM7A and Wnt1/β-catenin pathway-related proteins were determined by western blot analysis. Treatment of DNOP rats with LWDH could significantly ameliorate the general state, degradation of renal function, and renal pathological changes. LWDH decreased the levels of TNF-α, IL-6, IL-8, IL-1β, ALP, and TRAP, and increased the calcium, phosphorus in serum, as well as decreased the level of the calcium, phosphorus in the urine. Besides, LWDH significantly improved bone mineral density (BMD), bone volume (BV), and the bone microstructure of DNOP rats. Moreover, LWDH increased the levels of the elastic modulus, ultimate load, and bending strength in the femurs. In MC3T3-E1 cells, serum-containing LWDH significantly increases in cell viability and osteoblastic differentiation capability. The expression of α-SMA, vimentin, KDM7A, Wnt1, β-catenin, were significantly down-regulated, and the E-cadherin, H3K9-Me2, H3K27-Me2, BMP-4, BMP-7, Runx2, osteocalcin, and Col1a1 were significantly up-regulated with LWDH treatment. The present study shows that LWDH has a therapeutic effect on DNOP, in part, through down-regulation of KDM7A and Wnt/β-catenin pathway.

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Section: Discussionsupporting

confidence: 51%

“…It is established that EMT is a common and complicated pathological process observed in DN rats [ 24 ]. In the present study, LWDH treatment significantly decreased the expression of α-SMA and Vimentin levels and increased the level E-cadherin protein of rats after 12 weeks compared with the DNOP group.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis

et al. 2020

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“…EMT is a tightly regulated process by which epithelial cells lose their hallmark epithelial characteristics and gain the features of mesenchymal cells [44]. The main pathological change of DKD in the end stage is the appearance of renal interstitial fibrosis [45]. It is generally recognized that through EMT, the renal epithelial cells can be transformed into myofibroblasts, which are the main source of extracellular matrix in the kidney, thus participating in the process of DKD renal interstitial fibrosis [46,47].…”

Section: Discussionmentioning

confidence: 99%

DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose

et al. 2020

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Objective: This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism. Materials and Methods: From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay. Results: A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-a and IL-1b, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelialmesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results. Conclusion: These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD.

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“…Furthermore, the current study demonstrated the therapeutic effects of DMix in protecting renal function and preventing renal fibrosis. Gliquidone is a sulfonylurea-based hypoglycemic agent that can bind to the specific receptors on the pancreatic β cell membrane to promote insulin secretion; it has a certain protective effect on the kidney (35). Gliquidone is a commonly used drug in the clinical treatment of DN and was used as a positive control in the present study.…”

Section: Discussionmentioning

confidence: 99%

Dendrobium mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway

et al. 2021

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notable glomerular hypertrophy, an increase in mesangial matrix content and renal interstitial fibrosis. Moreover, DMix notably reduced kidney damage. The results demonstrated that DMix inhibited the phosphorylation of PI3K, Akt and mTOR in the kidney tissues of rats with DN, and increased the protein and mRNA expression levels of LC3 and Beclin-1. Therefore, it was suggested that DMix has protective effects on the kidney of rats with DN, which may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway and activation of renal autophagy by this traditional medicine.

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Gliquidone Alleviates Diabetic Nephropathy by Inhibiting Notch/Snail Signaling Pathway

Cited by 29 publications

References 30 publications

Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis

Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis

DACH1, a novel target of miR-218, participates in the regulation of cell viability, apoptosis, inflammatory response, and epithelial-mesenchymal transition process in renal tubule cells treated by high-glucose

Dendrobium mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway

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