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

2015 ◽  
Vol 35 (4) ◽  
pp. 1425-1436 ◽  
Author(s):  
Tingfang Chen ◽  
Li Yang Zheng ◽  
Wenzhen Xiao ◽  
Dingkun Gui ◽  
Xiaoxia Wang ◽  
...  
Keyword(s):  
High Glucose ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Option ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Mesenchymal Transition ◽  
Epithelial Marker

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.

scholarly journals Erythropoietin Inhibits Hypoxia–Induced Epithelial-To-Mesenchymal Transition via Upregulation of miR-200b in HK-2 Cells

2017 ◽  
Vol 42 (1) ◽  
pp. 269-280 ◽  
Author(s):  
Jiuxu Bai ◽  
Xiao Xiao ◽  
Xiaoling Zhang ◽  
Hanmin Cui ◽  
Junfeng Hao ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Tubular Epithelial Cell ◽  
Epithelial Cell Line ◽  
Protective Effects ◽  
Mesenchymal Transition ◽  
Proximal Tubular ◽  
Renal Tubular

Background/Aims: Renal tubular epithelial-mesenchymal transition (EMT) is regarded as an important factor leading to renal interstitial fibrosis. Erythropoietin (EPO) has been reported to attenuate renal fibrosis. The mechanism underlying this protective effect of EPO remains unclear. In this study, we aim to identify possible mechanisms of the EPO renoprotective effect. Methods: Hypoxia was induced in vitro by incubating human proximal tubular epithelial cell line HK-2 cells in 1% O2 and 5% CO2. Western blotting and reverse transcription polymerase chain reaction analyses were used to evaluate the expression of epithelial and mesenchymal markers in the cell samples. The expression of miR-200b in the HK-2 cells under hypoxia or treatment with EPO was examined. Results: EPO represses hypoxia-induced EMT by upregulating miR-200b in HK-2 cells. Overexpression of miR-200b represses the effect of ETS proto-oncogene 1 (Ets-1)-induced EMT in HK-2 cells. Conclusion: miR-200 mediates the protective effects of EPO on EMT in hypoxic HK-2 cells. EPO attenuated hypoxia-induced EMT by increasing miR-200 expression via the repression of Ets-1.

scholarly journals ROS Promote Hypoxia-Induced Keratinocyte Epithelial-Mesenchymal Transition by Inducing SOX2 Expression and Subsequent Activation of Wnt/β-Catenin

2022 ◽  
Vol 2022 ◽  
pp. 1-23
Author(s):  
Yan Shi ◽  
Shang Wang ◽  
Ronghua Yang ◽  
Zhenmin Wang ◽  
Weiwei Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Mesenchymal Transition ◽  
Sox2 Expression ◽  
Subsequent Activation ◽  
And Migration

We previously showed that wound-induced hypoxia is related to keratinocyte migration. The ability of keratinocytes within wound healing to undergo epithelial to mesenchymal transition (EMT) contributes significantly to the acquisition of migratory properties. However, the effect of hypoxia on keratinocyte EMT on wound healing and the potential mechanism are poorly documented. This study first demonstrated that reactive oxygen species (ROS) appear to be an essential signalling mediator in keratinocytes with increased EMT and migration subjected to hypoxic conditions. Next, we showed that the expression of sex-determining region Y-box 2 (SOX2), a stemness-associated molecule, is ROS-dependent under hypoxia and that SOX2 inhibition in keratinocytes dramatically prevented hypoxia-induced EMT and migration. In addition, β-catenin was found to be a potential molecular target of SOX2, and the activation of Wnt/β-catenin was required for hypoxia-induced EMT and migration. Using an in vitro skin culture model and an in vivo skin wound model, our study further reinforced the critical role of ROS in inducing EMT through SOX2 expression and subsequent activation of Wnt/β-catenin, allowing for rapid reepithelialization of the wound area. Taken together, our findings reveal a previously unknown mechanism by which hypoxia promotes wound healing by promoting reepithelialization through the production of ROS, inducing keratinocyte EMT and migration via the enhancement of SOX2 and activation of Wnt/β-catenin.

Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT

2016 ◽  
Vol 130 (16) ◽  
pp. 1469-1480 ◽  
Author(s):  
Kaiming Wu ◽  
Changhong Ye ◽  
Lin Lin ◽  
Yimin Chu ◽  
Meng Ji ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Fibrosis ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Option ◽  
Serum Marker ◽  
Mesenchymal Transition ◽  
Hepatic Fibrogenesis

MicroRNA-21 (miR-21) has emerged as a critical regulatory molecule and an important serum marker in hepatic fibrogenesis. The aim of the present study was to investigate the role of inhibiting miR-21 on hepatic fibrosis treatment. Serum miR-21 levels in 60 healthy individuals and 180 patients with different stages of liver cirrhosis were examined, miR-21 levels in normal or cirrhotic human liver tissues (n=10 each) were also detected. An adenoviral vector (Ad-TuD-21) carrying the sponging ToughDecoy (TuD)-RNA sequence against miR-21 was constructed to reduce miR-21 expression efficiently in vitro and in vivo. Histological and immunohistological examinations were performed to evaluate the inhibitory effects and mechanism of Ad-TuD-21 delivery into carbon tetrachloride (CCl4) induced hepatic fibrosis rats by targeting extracellular signal-regulated kinase 1 (ERK1) signalling in hepatic stellate cells (HSC) and hepatocyte epithelial–mesenchymal transition (EMT). Our results revealed that enhanced miR-21 levels in cirrhotic patients were related to the severity and activity of liver cirrhosis. Ad-TuD-21 administered to liver fibrosis rats could remarkably suppress profibrotic gene expression, cause histological improvements in liver and attenuate hepatic fibrosis significantly. More importantly, after Ad-TuD-21 treatment, inhibition of both the ERK1 signalling pathway in HSC and hepatocyte EMT was confirmed, which paralleled the enhancement of miR-21 target genes–sprouty2 (SPRY2) and hepatocyte nuclear factor 4α (HNF4α)–expression in vivo. These data demonstrated that miR-21 is a key regulator to promote hepatic fibrogenesis, and sponging miR-21 expression may present a novel potentially therapeutic option for hepatic fibrosis.

scholarly journals Ginsenoside Rg1 Alleviates Podocyte EMT Passage by Regulating AKT/GSK3 β/β-Catenin Pathway by Restoring Autophagic Activity

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yimin Shi ◽  
Yanbin Gao ◽  
Tao Wang ◽  
Xiaolei Wang ◽  
Jiaxin He ◽  
...  
Keyword(s):  
High Glucose ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Diabetic Rats ◽  
Ginsenoside Rg1 ◽  
Glomerular Diseases ◽  
Mesenchymal Transition ◽  
Glucose Levels ◽  
Autophagic Activity

Background. Diabetic nephropathy (DN), a complication of diabetes, is the result of high glucose-induced pathological changes in podocytes, such as epithelial-mesenchymal transition (EMT). Autophagy is an important mechanism of podocyte repair. Ginsenoside Rg1, the active ingredient of ginseng extract, has antifibrotic and proautophagic effects. Therefore, we hypothesized that ginsenoside Rg1 can reverse podocyte EMT via autophagy and alleviate DN. Aim. This study aimed to investigate the effect of ginsenoside Rg1 on DN rats and high glucose-induced podocyte EMT by regulating the AKT/GSK3β/β-catenin pathway by restoring autophagy activity. Methods. Diabetic rats induced by STZ injection were treated with 50 mg/kg ginsenoside Rg1 for 8 weeks, and the renal functional, metabolic, and histopathological indices were evaluated. DN was simulated in vitro by exposing podocytes to high glucose levels and treated with ginsenoside Rg1. The expression of EMT and autophagy-related markers was analyzed in vivo and in vitro by immunofluorescence, western blotting, and real-time PCR. Results. Ginsenoside Rg1 significantly alleviated renal fibrosis and podocyte EMT in diabetic rats, and podocytes exposed to high glucose levels, which was abolished by the autophagy inhibitor 3-MA. Furthermore, ginsenoside Rg1 regulated the AKT/GSK3 β/β-catenin pathway by restoring autophagic activity. Conclusion. Ginsenoside Rg1 alleviated podocyte EMT by enhancing AKT/GSK3β/β-catenin pathway-mediated autophagy, indicating its therapeutic potential for DN and other glomerular diseases.

scholarly journals TRAIL promotes epithelial-to-mesenchymal transition by inducing PD-L1 expression in esophageal squamous cell carcinomas

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Huanyu Zhang ◽  
Guohui Qin ◽  
Chaoqi Zhang ◽  
Huiyun Yang ◽  
Jinyan Liu ◽  
...  
Keyword(s):  
Western Blot ◽  
Squamous Cell ◽  
Mechanism Of Action ◽  
Epithelial To Mesenchymal Transition ◽  
Biological Function ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Mesenchymal Transition

Abstract Background Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) was initially considered an immunity guard; however, its function remains controversial. Besides immune cells, lung and colon cancer cells have also been reported to express TRAIL, which can promote tumor invasion and metastasis. However, the biological function and underlying mechanism of action of TRAIL in esophageal squamous cell carcinoma (ESCC) remain poorly elucidated. Methods The ESCC cells stemness, migration, and proliferation ability was assessed by sphere formation, Transwell, and CCK8 assay. The stemness- and epithelial-mesenchymal transition (EMT)- related genes expression levels were analyzed by Western blot and RT-qPCR. The signal activation was conducted by Western blot. The xenograft mouse experiments and lung metastasis model were performed to confirm our findings in vitro. Results Herein, we found that TRAIL is a negative predictor in patients with ESCC. To further investigate the biological function of TRAIL, we established TRAIL knockdown and overexpression ESCC cell lines and found that TRAIL induced EMT and promoted tumor aggressiveness. Furthermore, we demonstrated that TRAIL- overexpressing cells upregulated PD-L1 expression, which was dependent on the p-ERK/STAT3 signaling pathway. We obtained similar results when using recombinant human TRAIL. Finally, we validated the biological role and mechanism of action of TRAIL in vivo. Conclusions These findings demonstrate that TRAIL promotes ESCC progression by enhancing PD-L1 expression, which induces EMT. This may explain the failure of TRAIL preclinical trials.

scholarly journals Gene Expression Profiling Identifies ESRP1 as a Potential Regulator of Epithelial Mesenchymal Transition in Somatotroph Adenomas from a Large Cohort of Patients with Acromegaly

2012 ◽  
Vol 97 (8) ◽  
pp. E1506-E1514 ◽  
Author(s):  
Tove Lekva ◽  
Jens Petter Berg ◽  
Stine Lyngvi Fougner ◽  
Ole Kristoffer Olstad ◽  
Thor Ueland ◽  
...  
Keyword(s):  
Tumor Size ◽  
Epithelial Mesenchymal Transition ◽  
Poor Response ◽  
Gh3 Cells ◽  
Pcr Analysis ◽  
Mesenchymal Transition ◽  
Epithelial Marker ◽  
E Cadherin

Abstract Context: The epithelial marker E-cadherin plays a crucial role in epithelial-mesenchymal transition (EMT). Decreased protein content in somatotroph adenomas has been associated with increased tumor size, invasion, and poor response to somatostatin analog (SA) treatment, but the potential mechanisms of EMT progression in these adenomas are lacking. Objective: We hypothesized that characterization of EMT-related transcripts in somatotroph adenomas could identify novel therapeutic targets in individuals with poor response to SA treatment and provide more knowledge of the mechanism of EMT progression. Patients: Fifty-three patients with acromegaly participated in the study. Research Design and Methods: We performed microarray analysis of 16 adenomas, eight with high expression and eight with low expression of E-cadherin, in order to identify EMT-related transcripts. Candidate transcripts were further explored in vivo in 53 adenomas and in vitro in a rat pituitary GH-producing cell (GH3) after exploring three models for reducing E-cadherin and inducing a mesenchymal phenotype. Results: In vivo E-cadherin mRNA expression in tumor tissue is associated negatively with tumor size and invasiveness and positively with GH and IGF-I levels in serum and response to SA treatment. Microarray and subsequent PCR analysis identify several EMT-related genes associated with E-cadherin expression. In vitro, few of these EMT-related genes were regulated by silencing E-cadherin or by TGF-β1 treatment in GH3 cells. In contrast, silencing Esrp1 in GH3 cells regulated many of the EMT-related transcripts. Conclusion: These results indicate that ESRP1 could be a master regulator of the EMT process in pituitary adenomas causing acromegaly.

scholarly journals A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Liu ◽  
Cheng Zhang ◽  
Jizhao Wang ◽  
Xu Liu ◽  
Hangying Qu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Tissue ◽  
Transformation Rate ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis

Abstract Background Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo. Methods qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients’ cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth. Results LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume. Conclusion In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.

scholarly journals TRAIL Promotes Epithelial-to-mesenchymal Transition by Inducing PD-L1 Expression in Esophageal Squamous Cell Carcinomas

2020 ◽  
Author(s):  
Huanyu Zhang ◽  
Guohui Qin ◽  
Huiyun Yang ◽  
Jinyan Liu ◽  
Peng Wu ◽  
...  
Keyword(s):  
Western Blot ◽  
Squamous Cell ◽  
Mechanism Of Action ◽  
Epithelial To Mesenchymal Transition ◽  
Biological Function ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Mesenchymal Transition

Abstract Background: Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) was initially considered an immunity guard; however, its function remains controversial. Besides immune cells, lung and colon cancer cells have also been reported to express TRAIL, which can promote tumor invasion and metastasis. However, the biological function and underlying mechanism of action of TRAIL in esophageal squamous cell carcinoma (ESCC) remain poorly elucidated.Methods: The ESCC cells stemness, migration, and proliferation ability was assessed by sphere formation, Transwell, and CCK8 assay. The stemness- and EMT- related genes expression levels were analyzed by Western blot and RT-qPCR. The signal activation was conducted by Western blot. The PDX Model were performed to confirm our findings in vitro.Results: Herein, we found that TRAIL is a negative predictor in patients with ESCC. To further investigate the biological function of TRAIL, we established TRAIL knockdown and overexpression ESCC cell lines and found that TRAIL induced epithelial-mesenchymal transition (EMT) and promoted tumor aggressiveness. Furthermore, we demonstrated that TRAIL- overexpressing cells upregulated PD-L1 expression, which was dependent on the p-ERK/STAT3 signaling pathway. We obtained similar results when using recombinant human TRAIL. Finally, we validated the biological role and mechanism of action of TRAIL in vivo.Conclusions: These findings demonstrate that TRAIL promotes ESCC progression by enhancing PD-L1 expression, which induces EMT. This may explain the failure of TRAIL preclinical trials.Financial support: This work was supported by the National Key Research and Development (2018YFC1313400), the National Nature Science Foundation of China (U1804281, 91942314) and the National Science Fund for Distinguished Young Scholars (82001659).

scholarly journals ELK1 Promotes Epithelial-Mesenchymal Transition and the Progression of Lung Adenocarcinoma by Upregulating B7-H3

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Ting-ting Yu ◽  
Tao Zhang ◽  
Fei Su ◽  
Ying-long Li ◽  
Li Shan ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Transcriptional Regulator ◽  
Mesenchymal Transition ◽  
Poor Patient ◽  
Patient Prognosis

In previous studies, we found that B7 homolog 3 (B7-H3) was highly expressed in lung adenocarcinoma (LUAD) and promoted epithelial-to-mesenchymal transition (EMT) of LUAD cells. However, the underlying molecular mechanism is unclear. This study is aimed at evaluating the role of Ets-like protein 1 (ELK1) as a transcriptional regulator of B7-H3 for mediating the development and progression of LUAD in vitro and in vivo. We confirmed that ELK1 is highly expressed in LUAD and is associated with poor patient prognosis. ELK1 was found to promote proliferation, invasion, migration, and EMT of LUAD cells through in vivo and in vitro experiments. In terms of mechanism, ELK1 binds to the B7-H3 promoter region and induces the upregulation of B7-H3 in LUAD. Our data suggest that ELK1 plays an important role in the development of LUAD and could be used as a prognostic marker and therapeutic target for LUAD.

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