GSK-3� and Vitamin D Receptor are Involved in �-Catenin and Snail Signaling in High Glucose-Induced Epithelial-Mesenchymal Transition of Mouse Podocytes

Guo, Jia; Xia, Nannan; Yang, Lili; Zhou, Sijie; Zhang, Qian; Qiao, Ye; Liu, Zhangsuo

doi:10.1159/000358678

Cited by 33 publications

(29 citation statements)

References 36 publications

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“…Vitamin D analogs also induce the expression of E-cadherin, promoting translocation of β-catenin from the nucleus to the cell membrane, to control cell growth and differentiation [19]. In our study, we found that VDR could be downregulated by high glucose and take part in the epithelial-epithelial-mesenchymal transition of podocyte in mice [21].…”

Section: The Effect Of Vitamin D In Cell Proliferation and Differentisupporting

confidence: 51%

The Multiple Roles of Vitamin D Besides Calcium-Phosphorus Metabolism

Guo¹,

Liu²

2017

A Critical Evaluation of Vitamin D - Basic Overview

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Vitamin D is a kind of steroid hormone and is well known for its important role in regulating the levels of calcium (Ca) and phosphorus (P) as well as in mineralization of bone in body. But the vitamin D signaling also exhibits multiple effects, such as anti-inflammation effects, anticancer effect, and cardiovascular-and kidney-protective effects. From a practical point of view, vitamin D deficiency participates in many pathological progressions and diseases. In some diseases, the administration of vitamin D or vitamin D receptor agonist (VDRA) could rescue the clinical symptoms and improve outcomes. In this review, we briefly deal with these topics, limiting ourselves to comment on some novelty studies about vitamin D signaling, which might help us to understand the multiple effects of vitamin D in some pathological progresses and diseases, which are all worth to be studied further.

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Section: The Effect Of Vitamin D In Cell Proliferation and Differentisupporting

confidence: 51%

The Multiple Roles of Vitamin D Besides Calcium-Phosphorus Metabolism

Guo¹,

Liu²

2017

A Critical Evaluation of Vitamin D - Basic Overview

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“…β‐catenin signals is recognized as one of the cell signalling pathways involved in EMT 28. Next, we suggested weather DKK3 regulated EMT in pancreatic cancer by suppressed β‐catenin signalling in hypoxic conditions.…”

Section: Resultsmentioning

confidence: 83%

DKK3 blocked translocation of β‐catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc‐3 cell

Guo

Qin

2015

J Cellular Molecular Medi

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The Wnt/β‐catenin signalling pathway is activated in pancreatic cancer initiation and progression. Dickkopf‐related protein 3 (DKK3) is a member of the human Dickkopf family and an antagonist of Wnt ligand activity. However, the function of DKK3 in this pathway in pancreatic cancer is rarely known. We examined the expression of DKK3 in six human pancreatic cancer cell lines, 75 pancreatic cancer and 75 adjacent non‐cancerous tissues. Dickkopf‐related protein 3 was frequently silenced and methylation in pancreatic cancer cell lines (3/6). The expression of DKK3 was significantly lower in pancreatic cancer tissues than in adjacent normal pancreas tissues. Further, ectopic expression of DKK3 inhibits nuclear translocation of β‐catenin induced by hypoxia in pancreatic cancer Bxpc‐3 cell. The forced expression of DKK3 markedly suppressed migration and the stem cell‐like phenotype of pancreatic cancer Bxpc‐3 cell in hypoxic conditions through reversing epithelial–mesenchymal transition (EMT). The stable expression of DKK3 sensitizes pancreatic cancer Bxpc‐3 cell to gemcitabine, delays tumour growth and augments gemcitabine therapeutic effect in pancreatic cancer xenotransplantation model. Thus, we conclude from our finding that DKK3 is a tumour suppressor and improved gemcitabine therapeutic effect through inducing apoptosis and regulating β‐catenin/EMT signalling in pancreatic cancer Bxpc‐3 cell.

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“…Podocytes epithelial markers, such as nephrin and zonula occludens-1, are lost under diabetic condition, while mesenchymal cell markers, such as α-SMA and fibronectin are expressed, leading to podocyte dysfunction and proteinuria [25,26,27,28]. Recent study demonstrated that HG promoted podocyte EMT, as shown by decreased nephrin expression, and increased α-SMA expression [29]. In-vivo study further confirmed that in addition to loss of nephrin and zonula occludens-1, mesenchymal markers such as desmin, fibroblast-specific protein-1, and matrix metalloproteinase-9 could be observed in glomerular podocytes of diabetic nephropathy [21].…”

Section: Discussionmentioning

confidence: 99%

Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

Tingfang

Zheng

Xiao

et al. 2015

Cell Physiol Biochem

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Background: Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Methods: Conditionally immortalized mouse podocytes were exposed to HG with 30μg /ml of EMO and 1μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg^-1· d^-1 and QLT0267 at 10 mg· kg^-1· w^-1 p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. Results: HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. Conclusion: EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.

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GSK-3� and Vitamin D Receptor are Involved in �-Catenin and Snail Signaling in High Glucose-Induced Epithelial-Mesenchymal Transition of Mouse Podocytes

Cited by 33 publications

References 36 publications

The Multiple Roles of Vitamin D Besides Calcium-Phosphorus Metabolism

The Multiple Roles of Vitamin D Besides Calcium-Phosphorus Metabolism

DKK3 blocked translocation of β‐catenin/EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc‐3 cell

Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

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