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TGF-beta AND high glucose

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 impacts protein expression and cell signaling action that contributes to glycemic memory and irreversible progression of diabetic nephropathy (DN). We have demonstrated 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, GFR, mesangial cell expansion, collagen IV and TGF-β expression were significantly increased in diabetic Ins2(+/C96Y) mice compared to non-diabetic Ins2(+/+) mice and remained elevated despite glucose normalization with insulin implants...
September 1, 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
Tong Wang, Si-Si Chen, Rui Chen, De-Min Yu, Pei Yu
PURPOSE: Beta 2 glycoprotein I (β2GPI) has been shown the positive effect on diabetic atherosclerosis and retinal neovascularization. β2GPI can be reduced by thioredoxin-1, resulting in the reduced state of β2GPI. The possible protective effects of β2GPI and reduced β2GPI on diabetic nephropathy (DN) are not fully elucidated. The purpose of this study was to test a hypothesis that β2GPI and reduced β2GPI would improve DN in streptozotocin (STZ) induced diabetic mice and high-glucose (HG) exposed rat mesangial cell (RMC)...
2015: International Journal of Clinical and Experimental Medicine
Tong Wang, Si-Si Chen, Rui Chen, De-Min Yu, Pei Yu
PURPOSE: Beta 2 glycoprotein I (β2GPI) has been shown the positive effect on diabetic atherosclerosis and retinal neovascularization. β2GPI can be reduced by thioredoxin-1, resulting in the reduced state of β2GPI. The possible protective effects of β2GPI and reduced β2GPI on diabetic nephropathy (DN) are not fully elucidated. The purpose of this study was to test a hypothesis that β2GPI and reduced β2GPI would improve DN in streptozotocin (STZ) induced diabetic mice and high-glucose (HG) exposed rat mesangial cell (RMC)...
2015: International Journal of Clinical and Experimental Pathology
Wei Zhang, Shangxin Song, Fei Liu, Yi Liu, Yuanshu Zhang
BACKGROUND: Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, β-casomorphin-7 may exert anti-fibrotic activities in diabetic rats. However, the role of β-casomorphin-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, this study was designed to investigate the protective effect of β-casomorphin-7 on epithelial-mesenchymal transition (EMT) of NRK-52E cells treated under hyperglycemic condition and to explore the possible mechanism...
August 2015: Peptides
Jung Joo Yoon, Yun Jung Lee, So Min Lee, Dae Gill Kang, Ho Sub Lee
BACKGROUND: The pathological change of kidney in diabetic nephropathy is represented hypertrophy, inflammation, and renal fibrosis. Oryeongsan, traditional oriental herbal formula, is widely used for the treatment of nephrosis, dropsy, and uremia. This study was examined whether Oryeongsan attenuate high-glucose (HG)-promoted rat mesangial cell fibrosis and matrix accumulation, major features of diabetic glomerulosclerosis. METHODS: Oryeongsan was mixed traditional herbal medicine, Alisma orientale Juz, Polyporus umbellatus Fries, Atractylodes macrocephala Koidez, Poria cocos Wolf and Cinnamomum Cassia Presl (5:3:3:1)...
2015: BMC Complementary and Alternative Medicine
Melissa L Brown, Nathan Ungerleider, Lara Bonomi, Danielle Andrzejewski, Amy Burnside, Alan Schneyer
Emerging evidence suggests that activin with its associated receptors, second messengers, and antagonists would be excellent targets for therapeutic drug development in the treatment of diabetes. We undertook the current study to investigate the ability to extrapolate findings from rodent studies to human islets in which data thus far has been scarce. We tested the hypothesis that human islets synthesize activin and that activin participates in the regulation of islet β-cells. Human islets from 33 separate isolations were categorized based on functional status, culture status and diabetic status...
2014: Islets
Rokhsana Mortuza, Biao Feng, Subrata Chakrabarti
In diabetes, hyperglycaemia causes up-regulation of endothelin 1 (ET-1) and transforming growth factor beta 1 (TGF-β1). Previously we showed glucose reduces sirtuin1 (SIRT1), a class III histone deacetylase. Here, we investigated the regulatory role of SIRT1 on ET-1 and TGF-β1 expression. Human microvascular endothelial cells were examined following incubation with 25 mmol/l glucose (HG) and 5 mmol/l glucose (NG) with or without SIRT1 or histone acetylase p300 overexpression or knockdown. mRNA expressions of ET-1, TGF-β1, SIRT1, p300 and collagen 1α(I) were examined...
August 2015: Journal of Cellular and Molecular Medicine
María Lemini, Xarubet Ruiz-Herrera, María G Ledesma-Colunga, Nundehui Díaz-Lezama, Ericka A De Los Ríos, Fernando López-Barrera, Isabel Méndez, Gonzalo Martínez de la Escalera, Yazmín Macotela, Carmen Clapp
The levels of the hormone prolactin (PRL) are reduced in the circulation of patients with Type 2 diabetes and in obese children, and lower systemic PRL levels correlate with an increased prevalence of diabetes and a higher risk of metabolic syndrome. The secretion of anterior pituitary (AP) PRL in metabolic diseases may be influenced by the interplay between transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α), which inhibit and can stimulate AP PRL synthesis, respectively, and are known contributors to insulin resistance and metabolic complications...
May 1, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Fang Wang, E Albert Reece, Peixin Yang
OBJECTIVE: Oxidative stress plays a causal role in diabetic embryopathy. Maternal diabetes induces heart defects and impaired transforming growth factor beta (TGFβ) signaling, which is essential for cardiogenesis. We hypothesize that mitigating oxidative stress through superoxide dismutase 1 (SOD1) overexpression in transgenic (Tg) mice reverses maternal hyperglycemia-impaired TGFβ signaling and its downstream effectors. STUDY DESIGN: Day 12.5 embryonic hearts from wild-type (WT) and SOD1 overexpressing embryos of nondiabetic (ND) and diabetic mellitus (DM) dams were used for the detection of oxidative stress markers: 4-hydroxynonenal (4-HNE) and malondlaldehyde (MDA), and TGFβ1, 2, and 3, phosphor (p)-TGFβ receptor II (TβRII), p-phosphorylated mothers against decapentaplegic (Smad)2, and p-Smad3...
May 2015: American Journal of Obstetrics and Gynecology
Sabrina Ehnert, Thomas Freude, Christoph Ihle, Larissa Mayer, Bianca Braun, Jessica Graeser, Ingo Flesch, Ulrich Stöckle, Andreas K Nussler, Stefan Pscherer
Type 2 diabetes mellitus (T2DM) is one of the most frequent metabolic disorders in industrialized countries. Among other complications, T2DM patients have an increased fracture risk and delayed fracture healing. We have demonstrated that supraphysiological glucose and insulin levels inhibit primary human osteoblasts׳ maturation. We aimed at developing a more physiologically relevant in vitro model to analyze T2DM-mediated osteoblast changes. Therefore, SCP-1-immortalized pre-osteoblasts were differentiated with T2DM or control (non-obese and obese) sera...
March 15, 2015: Experimental Cell Research
Ahmed M Kabel, Maaly A Abd Elmaaboud, Ahmed A Albarraq
Non-alcoholic steatohepatitis (NASH) has a relation to obesity. It may lead to hepatocellular carcinoma. To date, the therapeutic options are limited due to complex pathogenesis. This study aimed to investigate the effect of atorvastatin and omega 3 fatty acids on experimentally-induced NASH. Sixty male albino rats were divided into 6 equal groups; control group, high fat emulsion/sucrose (HFE/S) diet, HFE/S+carboxymethyl cellulose, HFE/S +Atorvastatin, HFE/S+Fish oil and HFE/S+Atorvastatin+Fish oil. Serum alanine aminotransferase, total cholesterol (TC), triglycerides (TG), high density lipoproteins, insulin, glucose, C-reactive protein and quantitative insulin sensitivity check index were measured...
May 2015: Prostaglandins, Leukotrienes, and Essential Fatty Acids
E Passos, C D Pereira, I O Gonçalves, S Rocha-Rodrigues, N Silva, J T Guimarães, D Neves, A Ascensão, J Magalhães, M J Martins
AIMS: Pro-inflammatory mediators, glucocorticoids and transforming growth factor (TGF)-β are implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH)-related insulin resistance. As physical activity is beneficial against NASH, we analyzed the voluntary physical activity (VPA) and endurance training (ET) (preventive and therapeutic strategies) effects on hepatic insulin, pro-inflammatory and glucocorticoid signaling regulators/mediators in high-fat (Lieber-DeCarli) diet (HFD)-induced NASH...
February 15, 2015: Life Sciences
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