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https://www.readbyqxmd.com/read/27913625/absence-of-mir-146a-in-podocytes-increases-risk-of-diabetic-glomerulopathy-via-upregulation-of-erbb4-and-notch-1
#1
Ha Won Lee, Samia Q Khan, Shehryar Khaliqdina, Mehmet M Altintas, Florian Grahammer, Jimmy L Zhao, Kwihey Koh, Nicholas J Tardi, Mohd Hafeez Faridi, Terese Geraghty, David J Cimbaluk, Katalin Susztak, Luis F Moita, David Baltimore, Pierre-Louis Tharaux, Tobias B Huber, Matthias Kretzler, Markus Bitzer, Jochen Reiser, Vineet Gupta
Podocyte injury is an early event in diabetic kidney disease and is a hallmark of glomerulopathy. MicroRNA-146a (miR-146a) is highly expressed in many cell types under homeostatic conditions, and plays an important anti-inflammatory role in myeloid cells. However, its role in podocytes is unclear. Here, we show that miR-146a expression levels decrease in the glomeruli of patients with type 2 diabetes (T2D), which correlates with increased albuminuria and glomerular damage. MiR-146a levels are also significantly reduced in the glomeruli of albuminuric BTBR ob/ob mice, indicating its significant role in maintaining podocyte health...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27913437/surface-expression-of-tgf%C3%AE-docking-receptor-garp-promotes-oncogenesis-and-immune-tolerance-in-breast-cancer
#2
Alessandra Metelli, Bill X Wu, Caroline W Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27909303/conditional-knockout-of-n-wasp-in-mouse-fibroblast-caused-keratinocyte-hyper-proliferation-and-enhanced-wound-closure
#3
Neeraj Jain, Pazhanichamy Kalailingam, Kai Wei Tan, Hui Bing Tan, Ming Keat Sng, Jeremy Soon Kiat Chan, Nguan Soon Tan, Thirumaran Thanabalu
Neural-Wiskott Aldrich Syndrome Protein (N-WASP) is expressed ubiquitously, regulates actin polymerization and is essential during mouse development. We have previously shown that N-WASP is critical for cell-ECM adhesion in fibroblasts. To characterize the role of N-WASP in fibroblast for skin development, we generated a conditional knockout mouse model in which fibroblast N-WASP was ablated using the Cre recombinase driven by Fibroblast Specific Protein promoter (Fsp-Cre). N-WASP(FKO) (N-WASP(fl/fl); Fsp-cre) were born following Mendelian genetics, survived without any visible abnormalities for more than 1 year and were sexually reproductive, suggesting that expression of N-WASP in fibroblast is not critical for survival under laboratory conditions...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906182/bcl-3-regulates-tgf%C3%AE-signaling-by-stabilizing-smad3-during-breast-cancer-pulmonary-metastasis
#4
Xi Chen, Xinwei Cao, Xiaohua Sun, Rong Lei, Pengfei Chen, Yongxu Zhao, Yuhang Jiang, Jie Yin, Ran Chen, Deji Ye, Qi Wang, Zhanjie Liu, Sanhong Liu, Chunyan Cheng, Jie Mao, Yingyong Hou, Mingliang Wang, Ulrich Siebenlist, Y Eugene Chin, Ying Wang, Liu Cao, Guohong Hu, Xiaoren Zhang
Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905842/airway-smooth-muscle-cells-from-ovalbumin-sensitized-mice-show-increased-proliferative-response-to-tgf%C3%AE-1-due-to-up-regulation-of-smad3-and-tgf%C3%AE-rii
#5
Jianting Shi, Ming Chen, Lihua Ouyang, Linjie Huang, Xiaoling Lin, Wei Zhang, Ruiyun Liang, Zhiqiang Lv, Shanying Liu, Shanping Jiang
Transforming growth factor (TGF)-β1 is an important cytokine in airway remodeling in asthma. However, results of studies focusing on the effect of TGFβ1 on proliferation of airway smooth muscle cells (ASMCs) are controversial. This study aimed to elucidate the role of TGFβ1 signaling in the proliferation of ASMCs by establishing an allergic model that mimics airway remodeling in chronic asthma and cell culture. Cell proliferation was detected by viable cell counting and Cell Counting Kit (CCK)-8 analysis...
December 1, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/27904762/activin-receptor-like-kinases-a-diverse-family-playing-an-important-role-in-cancer
#6
REVIEW
Holli A Loomans, Claudia D Andl
The role and function of the members of the TGFβ superfamily has been a substantial area of research focus for the last several decades. During that time, it has become apparent that aberrations in TGFβ family signaling, whether through the BMP, Activin, or TGFβ arms of the pathway, can result in tumorigenesis or contribute to its progression. Downstream signaling regulates cellular growth under normal physiological conditions yet induces diverse processes during carcinogenesis, ranging from epithelial- to-mesenchymal transition to cell migration and invasion to angiogenesis...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903298/meal-rich-in-carbohydrate-but-not-protein-or-fat-reveals-adverse-immunometabolic-responses-associated-with-obesity
#7
Ehsan Parvaresh Rizi, Sonia Baig, Muhammad Shabeer, Yvonne Teo, Shao Feng Mok, Tze Ping Loh, Faidon Magkos, Sam Virtue, Antonio Vidal-Puig, E Shyong Tai, Chin Meng Khoo, Sue-Anne Toh
BACKGROUND: Obesity-related insulin resistance is linked to inflammation. Immunometabolic function differs between lean and obese subjects, but whether macronutrient composition of ingested meals affects these responses is not well known. We examined the effects of a single meal rich in fat, protein, or carbohydrate on immunometabolic responses. METHODS: Nine lean insulin sensitive (LIS) men and 9 obese insulin resistant (OIR) men ingested high-carbohydrate (HC), high-fat (HF) or high-protein (HP) mixed meals in random order...
December 1, 2016: Nutrition Journal
https://www.readbyqxmd.com/read/27903243/analysis-of-rna-expression-of-normal-and-cancer-tissues-reveals-high-correlation-of-cop9-gene-expression-with-respiratory-chain-complex-components
#8
Christina A Wicker, Tadahide Izumi
BACKGROUND: The COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9...
December 1, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27902739/degenerative-suspensory-ligament-desmitis-dsld-in-peruvian-paso-horses-is-characterized-by-altered-expression-of-tgf%C3%AE-signaling-components-in-adipose-derived-stromal-fibroblasts
#9
Wei Luo, John Sandy, Katie Trella, Daniel Gorski, Shuguang Gao, Jun Li, Sabrina Brounts, Jorge Galante, Anna Plaas
Equine degenerative suspensory ligament desmitis (DSLD) in Peruvian Paso horses typically presents at 7-15 years and is characterized by lameness, focal disorganization of collagen fibrils, and chondroid deposition in the body of the ligament. With the aim of developing a test for disease risk (that can be used to screen horses before breeding) we have quantified the expression of 76 TGFβ-signaling target genes in adipose-derived stromal fibroblasts (ADSCs) from six DSLD-affected and five unaffected Paso horses...
2016: PloS One
https://www.readbyqxmd.com/read/27899316/inhibition-or-ablation-of-transglutaminase-2-impairs-astrocyte-migration
#10
Alina Monteagudo, Changyi Ji, Abdullah Akbar, Jeffrey W Keillor, Gail V W Johnson
Astrocytes play numerous complex roles that support and facilitate the function of neurons. Further, when there is an injury to the central nervous system (CNS) they can both facilitate or ameliorate functional recovery depending on the location and severity of the injury. When a CNS injury is relatively severe a glial scar is formed, which is primarily composed of astrocytes. The glial scar can be both beneficial, by limiting inflammation, and detrimental, by preventing neuronal projections, to functional recovery...
November 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27899163/human-fetal-and-adult-epicardial-derived-cells-a-novel-model-to-study-their-activation
#11
Asja T Moerkamp, Kirsten Lodder, Tessa van Herwaarden, Esther Dronkers, Calinda K E Dingenouts, Fredrik C Tengström, Thomas J van Brakel, Marie-José Goumans, Anke M Smits
BACKGROUND: The epicardium, a cell layer covering the heart, plays an important role during cardiogenesis providing cardiovascular cell types and instructive signals, but becomes quiescent during adulthood. Upon cardiac injury the epicardium is activated, which includes induction of a developmental gene program, epithelial-to-mesenchymal transition (EMT) and migration. However, the response of the adult epicardium is suboptimal compared to the active contribution of the fetal epicardium to heart development...
November 29, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27895117/examining-crosstalk-among-transforming-growth-factor-%C3%AE-bone-morphogen-protein-and-wnt-pathways
#12
Adam D Coster, Curtis A Thorne, Lani F Wu, Steve J Altschuler
The integration of morphogenic signals by cells is not well understood. A growing body of literature suggests increasingly complex coupling among classically defined pathways. Given this apparent complexity, it is difficult to predict where, when or even whether crosstalk occurs. Here, we investigated pairs of morphogenic pathways, previously reported to have multiple points of crosstalk, which either do not share (TGFβ; and Wnt/β-catenin) or share (TGFβ; and BMP) core signaling components. Crosstalk was measured by the ability of one morphogenic pathway to cross-activate core transcription factors and/or target genes of another morphogenic pathway...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27894619/expression-of-pro-fibrotic-and-anti-fibrotic-molecules-in-dimethylnitrosamine-induced-hepatic-fibrosis
#13
Roberta Sferra, Antonella Vetuschi, Simona Pompili, Eugenio Gaudio, Silvia Speca, Giovanni Latella
BACKGROUND: Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins, produced by activated myofibroblasts which are modulated by both profibrotic and antifibrotic factors. OBJECTIVE: To evaluate in vivo the expression of pro-fibrotic molecules like avβ6 integrin, transforming growth factor-β (TGF-β), Smad3, connective tissue growth factor (CTGF) and mammalian target of Rapamycin (mTOR), as well as anti-fibrotic peroxisome proliferator-activated receptor-γ (PPARγ) in an experimental model of chronic hepatitis-associated fibrosis induced by intraperitoneal administration of dimethylnitrosamine (DMN) in mice...
November 11, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27894066/obesity-associated-extracellular-mtdna-activates-central-tgf%C3%AE-pathway-to-cause-blood-pressure-increase
#14
Alberto Ale, Yalin Zhang, Cheng Han, Dongsheng Cai
Hypothalamic inflammation was recently found to mediate obesity-related hypertension, but the responsible upstream mediators remain unexplored. In this study, we show that dietary obesity is associated with extracellular release of mitochondrial DNA (mtDNA) into the cerebrospinal fluid, and that central delivery of mtDNA mimics TGFβ excess to activate downstream signaling pathways. Physiological study reveals that central administration of mtDNA or TGFβ are both sufficient to cause hypertension in mice. Knockout of the TGFβ receptor in pro-opiomelanocortin neurons counteracts the hypertensive effect of not only TGFβ but mtDNA excess, while the hypertensive action of central mtDNA can be blocked pharmacologically by a TGFβ receptor antagonist or genetically by TGFβ receptor knockout...
November 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27893715/tgf%C3%AE-promotes-mesenchymal-phenotype-of-pancreatic-cancer-cells-in-part-through-epigenetic-activation-of-vav1
#15
P-H Huang, P-J Lu, L-Y Ding, P-C Chu, W-Y Hsu, C-S Chen, C-C Tsao, B-H Chen, C-T Lee, Y-S Shan, C-S Chen
The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27891769/exenatide-induces-an-increase-in-vasodilatory-and-a-decrease-in-vasoconstrictive-mediators
#16
Ajay Chaudhuri, Husam Ghanim, Antoine Makdissi, Kelly Green, Sanaa Abuaysheh, Manav Batra, Nitesh Kuhadiya, Paresh Dandona
In view of the known vasodilatory effects of GLP-1, and exenatide, we investigated the effects of exenatide on vasoactive factors. We analyzed blood samples and mononuclear cells (MNC) from a previous study collected after a single dose and following 12 weeks of exenatide or placebo treatment on a series of 24 patients with T2DM. Following exenatide, plasma concentrations of ANP, cGMP, cAMP increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNC increased significantly following single dose...
November 28, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27889684/human-milk-oligosaccharide-effects-on-intestinal-function-and-inflammation-after-preterm-birth-in-pigs
#17
Stine O Rasmussen, Lena Martin, Mette V Østergaard, Silvia Rudloff, Michael Roggenbuck, Duc Ninh Nguyen, Per T Sangild, Stine B Bering
: Human milk oligosaccharides (HMOs) may mediate prebiotic and anti-inflammatory effects in newborns. This is particularly important for preterm infants who are highly susceptible to intestinal dysfunction and necrotizing enterocolitis (NEC). We hypothesized that HMO supplementation of infant formula (IF) improves intestinal function, bacterial colonization and NEC resistance immediately after preterm birth, as tested in a preterm pig model. Mixtures of HMOs were investigated in intestinal epithelial cells and in preterm pigs (n=112) fed IF supplemented without (CON) or with a mixture of four HMOs (4-HMO) or >25 HMOs (25-HMO, 5-10 g/L given for 5 or 11 days)...
November 4, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27888193/conserved-and-novel-functions-of-programmed-cellular-senescence-during-vertebrate-development
#18
Hongorzul Davaapil, Jeremy P Brockes, Maximina H Yun
Cellular senescence, a form of stable cell cycle arrest traditionally associated with tumour suppression, has been recently found to occur during mammalian development. Here, we show that cell senescence is an intrinsic part of the developmental programme in amphibians. Programmed senescence occurs in specific structures at defined time-windows during amphibian development. It contributes to the physiological degeneration of the amphibian pronephros and to the development of the cement gland and oral cavity...
November 25, 2016: Development
https://www.readbyqxmd.com/read/27887732/expressions-of-pathologic-markers-in-prp-based-chondrogenic-differentiation-of-human-adipose-derived-stem-cells
#19
Arezou Pakfar, Shiva Irani, Hana Hanaee-Ahvaz
BACKGROUND: Optimization of the differentiation medium through using autologous factors such as PRP is of great consideration, but due to the complex, variable and undefined composition of PRP on one hand and lack of control over the absolute regulatory mechanisms in in vitro conditions or disrupted and different mechanisms in diseased tissue microenvironments in in vivo conditions on the other hand, it is complicated and rather unpredictable to get the desired effects of PRP making it inevitable to monitor the possible pathologic or undesired differentiation pathways and therapeutic effects of PRP...
November 12, 2016: Tissue & Cell
https://www.readbyqxmd.com/read/27885276/immunoregulation-by-members-of-the-tgf%C3%AE-superfamily
#20
WanJun Chen, Peter Ten Dijke
The transforming growth factor-β (TGFβ) superfamily is encoded by 33 genes and includes TGFβ, bone morphogenetic proteins (BMPs) and activins. Although TGFβ is well recognized as a crucial regulator of immune responses, the immunoregulatory functions of other TGFβ family members are less clear. However, recent evidence suggests that BMPs and activins have important roles in regulating immune responses. In this Review, we briefly outline the signalling pathways of the TGFβ superfamily and discuss new insights into the immunoregulatory functions of BMPs and activins in the context of infection, inflammation and cancer...
November 25, 2016: Nature Reviews. Immunology
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