scholarly journals The PI3K/Akt Signaling Pathway Mediates the High Glucose-Induced Expression of Extracellular Matrix Molecules in Human Retinal Pigment Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Dong Qin ◽  
Guo-ming Zhang ◽  
Xun Xu ◽  
Li-ya Wang
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathway ◽  
High Glucose ◽  
Retinal Pigment ◽  
Akt Signaling ◽  
Collagen Iv ◽  
Akt Signaling Pathway ◽  
Induced Expression ◽  
Rpe Cells ◽  
Extracellular Matrix Molecules

Prolonged hyperglycemia is an important risk factor of the pathogenesis of diabetic retinopathy (DR). Extracellular matrix molecules, such as fibronectin, collagen IV, and laminin, are associated with fibrotic membranes. In this study, we investigated the expression of fibronectin, collagen IV, and laminin in RPE cells under high glucose conditions. Furthermore, we also detected the phosphorylation of protein kinase B (Akt) under high glucose conditions in RPE cells. Our results showed that high glucose upregulated fibronectin, collagen IV, and laminin expression, and activated Akt in RPE cells. We also found that pretreatment with LY294002 (an inhibitor of phosphatidylinositol 3-kinase) abolished high glucose-induced expression of fibronectin, collagen IV, and laminin in RPE cells. Thus, high glucose induced the expression of fibronectin, collagen IV, and laminin through PI3K/Akt signaling pathway in RPE cells, and the PI3K/Akt signaling pathway may contribute to the formation of fibrotic membrane during the development of DR.

scholarly journals Gremlin in the Vitreous of Patients with Proliferative Diabetic Retinopathy and the Downregulation of Gremlin in Retinal Pigment Epithelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Dong Qin ◽  
Yan-rong Jiang ◽  
Zijun Meng
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Rpe Cells ◽  
Glucose Levels ◽  
Pigment Epithelial ◽  
Extracellular Matrix Molecules

Diabetic retinopathy (DR) is one of the most common causes of blindness globally. Proliferative DR (PDR), an advanced stage of DR, is characterized by the formation of fibrotic membranes at the vitreoretinal interface. The proliferation, migration, and secretion of extracellular matrix molecules in retinal pigment epithelial (RPE) cells contribute to the formation of fibrotic membranes in PDR. Gremlin has been reported to be upregulated in response to elevated glucose levels in the retina of diabetic rat and bovine pericytes. However, the role of gremlin in PDR remains unclear. In the present study, the vitreous concentrations of gremlin were significantly higher in the PDR (67.79±33.96) group than in the control (45.31±12.31) group, and high glucose levels induced the expression of gremlin in RPE cells. The elevated expression of extracellular matrix molecules, such as fibronectin and collagen IV, was significantly reduced by gremlin siRNA in human RPE cells under high-glucose conditions. Thus, gremlin may play a vital role in the development of PDR.

scholarly journals Occludin downregulation in high glucose is regulated by SSTR2 via the VEGF/NRP1/Akt signaling pathway in RF/6A cells

2017 ◽  
Vol 14 (2) ◽  
pp. 1732-1738 ◽  
Author(s):  
Mengling Li ◽  
Shuaiwei Wang ◽  
Songjiang Wang ◽  
Lei Zhang ◽  
Dongdong Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Mycobacterium tuberculosis-induced expression of Leukotactin-1 is mediated by the PI3-K/PDK1/Akt signaling pathway

2009 ◽  
Vol 29 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Jang-Eun Cho ◽  
Yoon Suk Kim ◽  
Sangjung Park ◽  
Sang-Nae Cho ◽  
Hyeyoung Lee
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Induced Expression

scholarly journals Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenchang Lv ◽  
Shengxuan Liu ◽  
Qi Zhang ◽  
Weijie Hu ◽  
Yiping Wu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Luciferase Reporter Gene ◽  
Migration Flow ◽  
Gene Assay

Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighted the roles of circRNAs in acting as miRNA sponges. However, up to date, the regulatory mechanism of circRNAs in the pathological process of keloids has rarely been reported. In this study, cell proliferation, cell migration, flow cytometry, western blotting, fluorescence in situ hybridization, dual-luciferase activity, and immunohistochemistry assays were applied to explore the roles and mechanisms of the circCOL5A1/miR-7-5p/Epac1 axis in the keloid. The therapeutic potential of circCOL5A1 was investigated by establishing keloid implantation models. The RT-qPCR result revealed that circCOL5A1 expression was obviously higher in keloid tissues and keloid fibroblasts. Subsequent cellular experiments demonstrated that circCOL5A1 knockdown repressed the proliferation, migration, extracellular matrix (ECM) deposition, whereas promoted cell apoptosis, through the PI3K/Akt signaling pathway. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that both circCOL5A1 and miR-7-5p were located in the cytoplasm. The luciferase reporter gene assay confirmed that exact binding sites were present between circCOL5A1 and miR-7-5p, as well as between miR-7-5p and Epac1. Collectively, the present study revealed that circCOL5A1 functioned as competing endogenous RNA (ceRNA) by adsorbing miR-7-5p to release Epac1, which contributed to pathological hyperplasia of keloids through activating the PI3K/Akt signaling pathway. Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids.

scholarly journals Antioxidant Blueberry Anthocyanins Induce Vasodilation via PI3K/Akt Signaling Pathway in High-Glucose-Induced Human Umbilical Vein Endothelial Cells

2020 ◽  
Vol 21 (5) ◽  
pp. 1575 ◽  
Author(s):  
Wuyang Huang ◽  
Ruth Paulina Hutabarat ◽  
Zhi Chai ◽  
Tiesong Zheng ◽  
Weimin Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
High Glucose ◽  
Umbilical Vein ◽  
Akt Signaling ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Peroxisome Proliferator ◽  
Akt Signaling Pathway ◽  
Peroxisome Proliferator Activated Receptor

Blueberries are rich in antioxidant anthocyanins. The hypotensive effects of blueberry anthocyanins in endothelial cells was investigated here. Pretreatment with blueberry anthocyanin extract, malvidin, malvidin-3-glucoside, and malvidin-3-galactoside significantly ameliorated high-glucose-induced damage by enhancing endogenous antioxidant superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), lowering reactive oxygen species (ROS) generation and NADPH oxidase isoform 4 (NOX4) expression, and increasing the cell vitalities. They also effectively induced a vasodilatory effect by increasing the vasodilator nitric oxide (NO) and its promoters endothelial NO synthase (eNOS) and peroxisome proliferator-activated receptor-γ (PPARγ) levels as well as by decreasing the vasoconstrictor angiotensin-converting enzyme (ACE), xanthine oxidase-1 (XO-1), and low-density lipoprotein (LDL) levels. The activation of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and the breakdown of protein kinase C zeta (PKCζ) pathway were involved in the bioactivities. The results indicated blueberry anthocyanins protected endothelial function against high-glucose (HG) injury via antioxidant and vasodilatory mechanisms, which could be promising molecules as a hypotensive nutraceutical for diabetes patients.

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