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TGF-beta AND high glucose

Fengyun Yu, Leilei Bing, Yanrong Xie, Wenjuan Yu
BACKGROUND: Dysfunction of pancreatic beta cells is related with type 2 diabetes mellitus. Dioscin, a natural steroid saponin, has many pharmacological effects. The aim of this study was to investigate the effects of dioscin on apoptosis of pancreatic beta cells induced by high glucose. METHODS: Pancreatic cell line RNAKT-15 was treated with 20 mM glucose with or without different concentrations of dioscin and viability and apoptosis of cells were measured. Western blot assay was used to measure the expression levels of some proteins such as phosphorylated glycogen synthase kinase 3β (GSK-3β) and β-catenin...
May 1, 2018: Clinical Laboratory
Xi Xie, Qing Chen, Jun Tao
Oxidative stress is the main cause of diabetic nephropathy (DN) progression. Nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling is a crucial cellular defense system to cope with oxidative stress. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid with remarkable antioxidative capacity. AST exerted renal protective in diabetic rats. This study aimed to determine whether AST could alleviate the pathological progress of DN by activating Nrf2/ARE signaling and diminishing the excessive oxidative stress and fibronectin (FN) accumulation in glomerular mesangial cells (GMCs) challenged with high glucose (HG)...
April 5, 2018: Marine Drugs
Claire Hills, Gareth William Price, Mark John Wall, Timothy John Kaufmann, Sidney Chi-Wai Tang, Wai Han Yiu, Paul Edward Squires
BACKGROUND/AIMS: Changes in cell-to-cell communication have been linked to several secondary complications of diabetes, but the mechanism by which connexins affect disease progression in the kidney is poorly understood. This study examines a role for glucose-evoked changes in the beta1 isoform of transforming growth factor (TGFβ1), on connexin expression, gap-junction mediated intercellular communication (GJIC) and hemi-channel ATP release from tubular epithelial cells of the proximal renal nephron...
2018: Cellular Physiology and Biochemistry
Pin Chen, Xiaozhi Shi, Xiangjin Xu, Yiyang Lin, Zhulin Shao, Rongdan Wu, Lihong Huang
AIMS: The aim of this study was to investigate the effects of liraglutide on renal injury and the renal expression of FoxO1 in type 2 diabetic rats. METHODS: Type 2 diabetic rats model was induced by a high-sugar and high-fat diet and intraperitoneal injection of low-dose Streptozotocin (STZ) (30 mg/kg). Five weeks after STZ injection, diabetic rats were randomly treated with or without subcutaneous injection of liraglutide (0.2 mg/kg/12 h) for eight weeks...
March 2018: Diabetes Research and Clinical Practice
Elin Hall, Marloes Dekker Nitert, Petr Volkov, Siri Malmgren, Hindrik Mulder, Karl Bacos, Charlotte Ling
BACKGROUND: Type 2 diabetes (T2D) is a complex disease characterised by chronic hyperglycaemia. The effects of elevated glucose on global gene expression in combination with DNA methylation patterns have not yet been studied in human pancreatic islets. Our aim was to study the impact of 48 h exposure to high (19 mM) versus control (5.6 mM) glucose levels on glucose-stimulated insulin secretion, gene expression and DNA methylation in human pancreatic islets. RESULTS: While islets kept at 5...
November 26, 2017: Molecular and Cellular Endocrinology
Yuanyuan Guo, Lin Sun, Li Xiao, Rong Gou, Yudong Fang, Yan Liang, Ruiqiang Wang, Ningjun Li, Fuyou Liu, Lin Tang
Peritoneal dialysis (PD)-associated peritoneal fibrosis is a chronic progress which induces ultrafiltration failure. It remains a challenge to prevent the progression of PD-associated fibrosis in clinic practice. Wnt/β-catenin pathway plays important role in many severe fibrotic diseases, here we investigated its contribution to the development of peritoneal damage. We isolated mesothelial cells (MC) from the effluent of PD patients and found that the expressions of Wnt1, Wnt5a, β-catenin, and LEF1 were increased in patients with more than 1-year PD compared with patients who just started with PD (<1 month)...
2017: Frontiers in Pharmacology
Eugene Lin, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Shih-Jen Tsai
The transforming growth factor-β (TGF-β) signaling pathway and its relevant genes have been correlated with an increased risk of developing various hallmarks of metabolic syndrome (MetS). In this study, we assessed whether the TGF-β signaling pathway-associated genes of SMAD family member 2 (SMAD2), SMAD3, SMAD4, transforming growth factor beta 1 (TGFB1), TGFB2, TGFB3, transforming growth factor beta receptor 1 (TGFBR1), and TGFBR2 are associated with MetS and its individual components independently, through complex interactions, or both in a Taiwanese population...
October 19, 2017: Scientific Reports
Lu Bai, Beibei Huo, Zhiqiang Chen, Qian Guo, Jing Xu, Jing Fang, Jianghua Zhang, Fenfang Zhang
The study investigated the expression of Wnt/β-catenin pathway in diabetic rats and the intervention effect of Huayu Tongluo herbs (HTH). Ten rats were randomly selected as control group and the remaining rats were established as diabetic models. The diabetic rats were randomly divided into model group and HTH treatment group. The intervention was intragastric administration in all rats for 20 weeks. At the end of every 4 weeks, fasting blood glucose and 24 h urinary total protein quantitatively were measured...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Yuan Qiao, Ke Gao, Yangwei Wang, Xueliang Wang, Bo Cui
Resveratrol (RSV) has been shown to have a renoprotective effect against diabetic nephropathy, but the underlying mechanisms of this have not been fully elucidated. The aim of the current study was to explore the mechanisms responsible for the therapeutic effects of RSV in rat mesangial cells in vitro and in a rat model of diabetic nephropathy. The viability of CRL-2573 rat mesangial cells and their expression levels of p38, phosphorylated (p)-p38, transforming growth factor beta 1 (TGF-β1) and fibronectin were assessed in response to treatment with high glucose, with or without RSV...
June 2017: Experimental and Therapeutic Medicine
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications such as insulin resistance and non-alcoholic fatty liver disease are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
June 2, 2017: Journal of Biological Chemistry
Brijesh Sutariya, Madhusudan Saraf
ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Opuntia elatior Mill are being used traditionally in different disease condition like diabetes, obesity, asthma, inflammatory disorders, and anemia. Betanin, a compound isolated from fruits of Opuntia elatior Mill has potent anti-oxidative and anti-inflammatory activity. Recent study from our lab indicated the protective effect of betanin against high glucose induced rat renal epithelial cell fibrosis and matrix accumulation, major features of diabetic nephropathy (DN)...
February 23, 2017: Journal of Ethnopharmacology
Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
Mei Zhao, Lei Zhang, Lin Liu, Ya Li, Di Wang, Yi-Hui Li, Zhi-Hao Wang, Wei Zhang, Yun Zhang, Ming Zhong, Meng-Xiong Tang
BACKGROUND: Renal fibrosis is a process of excess accumulation and deposition of extracellular matrix (ECM) proteins in kidney. Transforming growth factor-beta (TGF-β) plays a vital role in accumulation of ECM through initiating phosphorylated Smad2/3. Whether activin receptor-like kinase 7 (ALK7), a member of TGF-β superfamily, was involved in renal interstitial fibrosis remains unclear. The aim of this study was to investigate whether ALK7 participates in renal fibrosis via regulating phosphorylated Smad2/3 in high-fat diet (HFD) rats...
September 13, 2016: Biochemical and Biophysical Research Communications
Farah Lizotte, Benoit Denhez, Andréanne Guay, Nicolas Gévry, Anne Marie Côté, Pedro Geraldes
Poor glycemic control profoundly affects protein expression and the cell signaling action that contributes to glycemic memory and irreversible progression of diabetic nephropathy (DN). We demonstrate that SHP-1 is elevated in podocytes of diabetic mice, causing insulin unresponsiveness and DN. Thus, sustained SHP-1 expression caused by hyperglycemia despite systemic glucose normalization could contribute to the glycemic memory effect in DN. Microalbuminuria, glomerular filtration rate, mesangial cell expansion, and collagen type IV and transforming growth factor-β expression were significantly increased in diabetic Ins2(+/C96Y) mice compared with nondiabetic Ins2(+/+) mice and remained elevated despite glucose normalization with insulin implants...
December 2016: Diabetes
Zhiying Yang, Fengxiao Xiong, Yu Wang, Wenyan Gong, Junying Huang, Cheng Chen, Peiqing Liu, Heqing Huang
Glucose and lipid metabolism disorders and chronic inflammation in the kidney tissues are largely responsible for causative pathological mechanism of renal fibrosis in diabetic nephropathy (DN). As our previous findings confirmed that, sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 2 (S1P2) signaling activation promoted renal fibrosis in diabetes. Numerous studies have demonstrated that the G protein-coupled bile acid receptor TGR5 exhibits effective regulation of glucose and lipid metabolism and anti-inflammatory effects...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Pan Gao, Yingze Wei, Zhigang Zhang, Wenjiao Zeng, Daming Sun, Danyang Liu, Bo Hou, Congying Zhang, Nong Zhang, Hui Li, Liliang Li
Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Transforming growth factor beta 1 (TGFβ1) is a well-distinguished mediator of progressive renal fibrosis in DN. However, the molecular mechanisms contributing to enhanced TGFβ1 expression in the progression of DN are not fully understood. Herein, we reported that c-Jun and specificity protein 1 (SP1) were critical upstream regulators of TGFβ1 expression in DN. The increase in c-Jun and SP1 expressions was positively correlated with TGFβ1 in both high glucose-treated human renal mesangial cells (HRMCs) and diabetic kidneys...
June 2016: Experimental and Molecular Pathology
Shukun Zhang, Menglan Zhang, Hong Huang, Shiying Zhou, Yanshneg Du, Xin Yi, Junming Luo
This study aimed at evaluating the effect of high glucose on the expression of extracellular matrix (ECM) protein Matrilin-2 and the mechanism underlying this effect by using a mouse mesangial cell line. Mouse mesangial cells (MMCs) were cultured in media containing normal (5 mM d-glucose) or high concentrations of glucose (30 mM d-glucose). The expression of Matrilin-2 was assessed by either RT-PCR or western blot. Additionally, transforming growth factor beta 1 (TGF-β1) inhibitors and TGF-β1 were used to determine whether glucose-regulated Matrilin-2 expression was mediated by the TGF-β1/Smad3 signaling pathway...
May 27, 2016: Biochemical and Biophysical Research Communications
Shu Li, Yun Hong, Xin Jin, Genbao Zhang, Zaichang Hu, Liuwang Nie
AIM: To assess the effects of protein C activator (PCA) from Agkistrodon halys snake venom on cardiac fibrosis in streptozotocin (STZ) induced diabetic rat model, and investigate the mechanisms of its action. METHODS: PCA was identified by one-dimensional reversed phase liquid chromatography - mass spectrometry/mass spectrometry. Male Sprague-Dawley rats (120-140 g) were randomly assigned to negative control (NC) and diabetic group. Diabetes was induced by STZ in high-fat diet fed rats...
October 2015: Croatian Medical Journal
Na Mi, Xiu Juan Zhang, Yan Ding, Guo Hua Li, Wei Dong Wang, Hui Xia Xian, Jin Xu
Diabetic nephropathy (DN) is the most severe diabetic microvascular complication. The pathogenesis of diabetic nephropathy is complex, and oxidative stress plays an important role in the development of diabetic nephropathy. Elevated reactive oxygen species (ROS) levels activate various signaling pathways and influence the activities of transforming growth factor-β (TGF-β) and matrix metalloproteinase-9 (MMP-9), which contributes to glomerular hypertrophy. Branched-chain amino acids (BCAAs) are widely used in clinical treatment, and BCAAs can reduce the oxidative stress associated with the diabetic pancreas and some liver diseases...
October 16, 2015: Biochemical and Biophysical Research Communications
Amjid Ahad, Haseeb Ahsan, Mohd Mujeeb, Waseem Ahmad Siddiqui
Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase, plays an important role in tissue inflammation and is known to be activated under conditions of oxidative stress and hyperglycemia. The role of p38 MAPK has been demonstrated in DN, and its inhibition has been suggested as an alternative approach in the treatment of DN. In the present study, we investigated the nephroprotective effects of an anti-inflammatory phenolic compound, gallic acid (GA, 3,4,5-trihydroxybenzoic acid), in high fat diet/streptozotocin (HFD/STZ) induce type 2 diabetic wistar albino rats...
October 5, 2015: Chemico-biological Interactions
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