scholarly journals MicroRNA-183 inhibition exerts suppressive effects on diabetic retinopathy by inactivating BTG1-mediated PI3K/Akt/VEGF signaling pathway

2019 ◽  
Vol 316 (6) ◽  
pp. E1050-E1060 ◽  
Author(s):  
Zhen-Zhen Zhang ◽  
Xiu-Hong Qin ◽  
Jing Zhang
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cells ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway

Diabetic retinopathy (DR) is a serious diabetic complication caused by both environmental and genetic factors. Molecular mechanisms of DR may lead to the discovery of reliable prognostic indicators. The current study aimed to clarify the mechanism of microRNA-183 (miR-183) in DR in relation to the PI3K/Akt/VEGF signaling pathway. Microarray-based gene expression profiling of DR was used to identify the differentially expressed genes. Sprague-Dawley rats were used for the establishment of DR models, and then miR-183 was altered by mimic or inhibitor or BTG1 was downregulated by siRNA to explore the regulatory mechanism of miR-183 in DR. Furthermore, the expression of miR-183, CD34, endothelial nitric oxide synthase (eNOS), BTG1 and the PI3K/Akt/VEGF signaling pathway-related genes as well as reactive oxygen species (ROS) level was determined, and the relationship between miR-183 and BTG1 was also verified. Cell growth, cell apoptosis, and angiogenesis were determined. Microarray analysis revealed the involvement of miR-183 in DR via the PI3K/Akt/VEGF signaling pathway by targeting BTG1. Upregulated miR-183 and downregulated BTG1 were observed in retinal tissues of DR rats. miR-183 overexpression activated the PI3K/Akt/VEGF signaling pathway, upregulated CD34, eNOS, and ROS, and inhibited BTG1. BTG1 was confirmed as a target gene of miR-183. miR-183 overexpression or BTG1 knockdown promoted cell growth and tube formation while it suppressed cell apoptosis of vascular endothelial cells in DR rats. In this study, we demonstrated that miR-183 silencing inhibiting cell growth and tube formation in vascular endothelial cells of DR rats via the PI3K/Akt/VEGF signaling pathway by upregulating BTG1.

scholarly journals Celastrol inhibits the proliferation and angiogenesis of high glucose-induced human retinal endothelial cells

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jian Fang ◽  
Xiaoke Chang
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
High Glucose ◽  
Microvascular Complications ◽  
Tube Formation ◽  
Immunofluorescence Assay ◽  
Retinal Endothelial Cells ◽  
Vegf Signaling ◽  
Qpcr Analysis ◽  
Vegf Signaling Pathway

Abstract Background Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. Celastrol plays a certain role in the improvement of various diabetes complications. Therefore, this study aimed to explore whether celastrol inhibited the proliferation and angiogenesis of high glucose (HG)-induced human retinal endothelial cells (hRECs) by down-regulating the HIF1/VEGF signaling pathway. Methods The viability and proliferation of hRECs treated with glucose, celastrol or dimethyloxallyl glycine (DMOG) were analyzed by MTT assay. The invasion and tube formation ability of hRECs treated with glucose, celastrol or DMOG were in turn detected by transwell assay and tube formation assay. The expression of HIF1α and VEGF in hRECs after indicated treatment was analyzed by Western blot analysis and RT-qPCR analysis and ICAM-1 expression in hRECs after indicated treatment was detected by immunofluorescence assay Results HG induction promoted the proliferation, invasion and tube formation ability and increased the expression of HIF-1α and VEGF of hRECs, which were gradually suppressed by celastrol changing from 0.5 to 2.0 μM. DMOG was regarded as a HIF1α agonist, which attenuated the effect of celastrol on HG-induced hRECs. Conclusion Celastrol inhibited the proliferation and angiogenesis of HG-induced hRECs by down-regulating the HIF1α/VEGF signaling pathway.

Overexpression of histone deacetylase SIRT1 exerts an antiangiogenic role in diabetic retinopathy via miR-20a elevation and YAP/HIF1α/VEGFA depletion

2020 ◽  
Vol 319 (5) ◽  
pp. E932-E943
Author(s):  
Qintuo Pan ◽  
Zhiqiang Gao ◽  
Chenlei Zhu ◽  
Zijie Peng ◽  
Minmin Song ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
Catalytic Activity ◽  
Histone Deacetylases ◽  
Vascular Endothelial Cells ◽  
Cell Number ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Vascular Endothelial ◽  
Class Iii

As a basic member of the Class III histone deacetylases, SIRT1 has been implicated in the occurrence and progression of diabetic retinopathy (DR). The current study aimed to investigate the roles of SIRT1/miR-20a/Yse-associated protein (YAP)/hypoxia-inducible factor 1 α (HIF1α)/vascular endothelial growth factor A (VEGFA) in DR. The expression of SIRT1 was initially determined through quantitative RT-PCR and Western blot analysis following the successful establishment of a DR mouse model, followed by detection of SIRT1 catalytic activity. Retinal microvascular endothelial cells (RMECs) were cultured in media supplemented with normal glucose (NG) or high glucose (HG). Thereafter, SIRT1 was either silenced or overexpressed in RMECs, after which EdU staining and Matrigel-based tube formation assay were performed to assess cell proliferation and tube formation. The binding relationship between YAP, HIF1α, and VEGFA was further illustrated using dual-luciferase reporter assay. Preretinal neovascular cell number was tallied with the IB4-positive vascular endothelial cells, as determined by immunofluorescence. SIRT1 was poorly expressed in mice with DR and HG-treated RMECs with low catalytic activity. The proliferation and tube formation capabilities of RMECs were elevated under HG conditions, which could be reversed following overexpression of SIRT1. SIRT1 was identified as positively regulating the expression of miR-20a with YAP detected as the key target gene of miR-20a. Our data suggested that YAP could upregulate VEGFA via induction of HIF1α. Moreover, SIRT1 overexpression strongly repressed RMEC proliferation and angiogenesis, which could be reversed via restoration of YAP/HIF1α/VEGFA expression. Taken together, the key findings of our study suggest that upregulation of SIRT1 inhibits the development of DR via miR-20a-induced downregulation of YAP/HIF1α/VEGFA.

scholarly journals The mTOR/AP-1/VEGF signaling pathway regulates vascular endothelial cell growth

Oncotarget ◽  
2016 ◽  
Vol 7 (33) ◽  
pp. 53269-53276 ◽  
Author(s):  
Shuo Wang ◽  
Jiawei Lu ◽  
Qingsheng You ◽  
Hua Huang ◽  
Yingying Chen ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Endothelial Cell Growth ◽  
Vegf Signaling Pathway

scholarly journals Tricyclic antidepressant amitriptyline inhibits autophagic flux and prevents tube formation in vascular endothelial cells

2018 ◽  
Vol 124 (4) ◽  
pp. 370-384 ◽  
Author(s):  
Yinglu Guan ◽  
Xiang Li ◽  
Michihisa Umetani ◽  
Krishna M. Boini ◽  
Pin‐Lan Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Tube Formation ◽  
Tricyclic Antidepressant ◽  
Autophagic Flux ◽  
Vascular Endothelial

scholarly journals Salmonella Typhimurium L Forms Induce Vascular Endothelial Cell Apoptosis via Mitochondrial-dependent Pathway

2021 ◽  
Author(s):  
Jinhai Zhai ◽  
Cuiping Yang ◽  
Tao Zhang ◽  
Dengyu Chen
Keyword(s):  
Endothelial Cells ◽  
Salmonella Typhimurium ◽  
Cell Apoptosis ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Intestinal Lumen ◽  
Vascular Endothelial ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Significant Difference

Abstract BackgroundSalmonella typhimurium is a pathogenic gram-negative bacterium, which is found primarily in the intestinal lumen. It often causes diarrhea in infants and young children and leads to food poisoning, as well as septicemia and septic shock. In this study, we investigated the phenomenon and mechanism of vascular endothelial cells apoptosis induced by Salmonella typhimurium L forms, in order to recognize and control Salmonella typhimurium L-form infection.Methods The apoptosis of vascular endothelial cells at 8 hours after infection with Salmonella typhimurium L forms was determined by flow cytometric assay and fluoroscopy of Annexin V-FITC/PI staining. Caspase-9 was detected by spectrophotometer. Results Salmonella typhimurium L forms can induce apoptosis of vascular endothelial cells, with significant difference in the apoptosis rate compared with the control. Caspase-9 expression is higher than that of the control. Conclusion The ability to induce cell apoptosis of vascular endothelial cells by Salmonella typhimurium L forms may be related to mitochondria apoptosis pathway depending on Caspase-9.

YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis Through Activating Yap Signaling in Vascular Endothelial Cells

2020 ◽  
Author(s):  
Yu Yan ◽  
Qiang Song ◽  
Li Yao ◽  
Liang Zhao ◽  
Hui Cai
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Tumor Angiogenesis ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Tissue Growth ◽  
Vascular Endothelial ◽  
Potential Marker

Abstract Background:The YAP signaling pathway is altered and implicated as oncogenic in human mammary cancers.However, roles of YAP signaling that regulate the breast tumor angiogenesis have remained elusive. Tumor angiogenesis is coordinated by the activation of both cancer cells and vascular endothelial cells. Whether the YAP signalingpathway can regulate the intercellular interaction between cancer cells and endothelial cellsis essentially unknown.Results: We showed here that conditioned media from YAP overexpressed breast cancer cells (CM-YAP+) could promote angiogenesis, accompanied byincreased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). Down regulation of YAP in HUVECs reversed CM-YAP+ induced angiogenesis.CM-YAP+ time-dependently activated YAP inHUVECs by dephosphorylating YAP and increasing nuclear translocation.We also identified that both G13-RhoA and PI3K/Akt signaling pathway were necessary for CM-YAP+ induced activation of YAP.Besides, connective tissue growth factor (CTGF) and angiopoietin-2 (ANG-2)actedas down-stream of YAP in HUVECs to promote angiogenesis.In addition, subcutaneous tumors nude mice model demonstrated that tumors overexpressed YAP revealed moreneovascularization in vivo.Conclusions: YAP-YAP interaction between breastcancer cells and endothelial cellscould promote tumor angiogenesis, supporting that YAP is a potential marker and target fordeveloping novel therapeutic strategies against breast cancer.

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