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FGF Receptor

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https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#1
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28523267/a-novel-role-for-the-bmp-antagonist-noggin-in-sensitizing-cells-to-non-canonical-wnt-5a-ror2-disheveled-pathway-activation
#2
Ondrej Bernatik, Tomasz Radaszkiewicz, Martin Behal, Zankruti Dave, Florian Witte, Annika Mahl, Nicole H Cernohorsky, Pavel Krejci, Sigmar Stricker, Vitezslav Bryja
Mammalian limb development is driven by the integrative input from several signaling pathways; a failure to receive or a misinterpretation of these signals results in skeletal defects. The brachydactylies, a group of overlapping inherited human hand malformation syndromes, are mainly caused by mutations in BMP signaling pathway components. Two closely related forms, Brachydactyly type B2 (BDB2) and BDB1 are caused by mutations in the BMP antagonist Noggin (NOG) and the atypical receptor tyrosine kinase ROR2 that acts as a receptor in the non-canonical Wnt pathway...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28515153/differential-regulation-of-renal-klotho-and-fgfr1-in-normal-and-uremic-rats
#3
Juan R Muñoz-Castañeda, Carmen Herencia, Maria Victoria Pendón-Ruiz de Mier, Maria Encarnación Rodriguez-Ortiz, Juan M Diaz-Tocados, Noemi Vergara, Julio M Martínez-Moreno, Maria Dolores Salmerón, William G Richards, Arnold Felsenfeld, Makoto Kuro-O, Yolanda Almadén, Mariano Rodríguez
In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28514740/differential-expression-of-circulating-biomarkers-of-tumor-phenotype-and-outcomes-in-previously-treated-non-small-cell-lung-cancer-patients-receiving-erlotinib-vs-cytotoxic-chemotherapy
#4
Mary Jo Fidler, Casey Frankenberger, Richard Seto, Gabriela C Lobato, Cristina L Fhied, Selina Sayidine, Sanjib Basu, Mark Pool, Reem Karmali, Marta Batus, Wen-Rong Lie, David Hayes, Jehangir Mistry, Philip Bonomi, Jeffrey A Borgia
BACKGROUND: The objective of this study was to identify serum biomarkers capable of predicting clinical outcomes in previously-treated NSCLC patients with wild-type for EGFR activating mutations or insufficient tissue for mutation status determination. METHODS: Sixty-six Luminex immunoassays representative of biological themes that emerged from a re-analysis of transcriptome data from the Cancer Genome Atlas (TCGA) were evaluate against pretreatment serum specimens from previously-treated advanced NSCLC patients received either cytotoxic chemotherapy (n=32) or erlotinib (n=79)...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512310/fgf23-fgfr4-mediated-left-ventricular-hypertrophy-is-reversible
#5
Alexander Grabner, Karla Schramm, Neerupma Silswal, Matt Hendrix, Christopher Yanucil, Brian Czaya, Saurav Singh, Myles Wolf, Sven Hermann, Jörg Stypmann, Giovana Seno Di Marco, Marcus Brand, Michael J Wacker, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone that directly targets cardiac myocytes via FGF receptor (FGFR) 4 thereby inducing hypertrophic myocyte growth and the development of left ventricular hypertrophy (LVH) in rodents. Serum FGF23 levels are highly elevated in patients with chronic kidney disease (CKD), and it is likely that FGF23 directly contributes to the high rates of LVH and cardiac death in CKD. It is currently unknown if the cardiac effects of FGF23 are solely pathological, or if they potentially can be reversed...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28502613/generation-of-a-targeted-expression-system-for-branchless-and-characterization-of-novel-cellular-expression-patterns-of-the-gene-in-drosophila
#6
Lijuan Du, Amy Zhou, Akshay Patel, Mishal Rao, Kelsey Anderson, Sougata Roy
Fibroblast growth factors (FGF) are essential signaling proteins that regulate diverse cellular functions in developmental and metabolic processes. In Drosophila, the FGF homolog, branchless (bnl) is expressed in a dynamic and spatiotemporally restricted pattern to induce branching morphogenesis of the trachea, which expresses the Bnl-receptor, breathless (btl). Here we have developed a new strategy to determine bnl- expressing cells and study their interactions with the btl-expressing cells in the range of tissue patterning during Drosophila development...
May 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28499383/nintedanib-antiangiogenic-inhibitor-effectiveness-in-delaying-adenocarcinoma-progression-in-transgenic-adenocarcinoma-of-the-mouse-prostate-tramp
#7
Raquel Frenedoso da Silva, Ellen Nogueira-Pangrazi, Larissa Akemi Kido, Fabio Montico, Sarah Arana, Dileep Kumar, Komal Raina, Rajesh Agarwal, Valéria Helena Alves Cagnon
BACKGROUND: In recent times, anti-cancer treatments have focused on Fibroblast Growth Factor (FGF) and Vascular-Endothelial Growth Factor (VEGF) pathway inhibitors so as to target tumor angiogenesis and cellular proliferation. One such drug is Nintedanib; the present study evaluated the effectiveness of Nintedanib treatment against in vitro proliferation of human prostate cancer (PCa) cell lines, and growth and progression of different grades of PCa lesions in pre-clinical PCa transgenic adenocarcinoma for the mouse prostate (TRAMP) model...
May 12, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28487440/cholestyramine-treatment-of-healthy-humans-rapidly-induces-transient-hypertriglyceridemia-when-treatment-is-initiated
#8
Beatrice Sjöberg, Sara Straniero, Bo Angelin, Mats Rudling
Bile acid (BA) production in mice is regulated by hepatic farnesoid X receptors and by intestinal fibroblast growth factor (FGF) 15, (in humans FGF19) a suppressor of BA synthesis that also reduces serum triglycerides and glucose. Cholestyramine treatment reduces FGF19 and induces BA synthesis while plasma triglycerides may increase of unclear reasons. We explored if FGF19 may suppress BA synthesis and plasma triglycerides in humans by modulation of FGF19 levels through long-term cholestyramine at increasing doses...
May 9, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28487375/pulmonary-fibrosis-requires-cell-autonomous-mesenchymal-fibroblast-growth-factor-fgf-signaling
#9
Robert D Guzy, Ling Li, Craig Smith, Samuel J Dorry, Hyun Young Koo, Lin Chen, David M Ornitz
Idiopathic Pulmonary Fibrosis (IPF) is characterized by progressive pulmonary scarring, decline in lung function, and often results in death within three to five years after diagnosis. Fibroblast Growth Factor (FGF) signaling has been implicated in the pathogenesis of IPF; however, the mechanism through which FGF signaling contributes to pulmonary fibrosis remains unclear. We hypothesized that FGF receptor (FGFR) signaling in fibroblasts is required for the fibrotic response to bleomycin. To test this, mice with mesenchyme-specific tamoxifen-inducible inactivation of FGF receptors 1, 2, and 3 (Col1α2-CreER; TCKO mice) were lineage labeled and administered intratracheal bleomycin...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28483978/fgf-dependent-context-driven-role-for-frs-adapters-in-the-early-telencephalon
#10
Sayan Nandi, Grigoriy Gutin, Christopher A Blackwood, Nachiket G Kamatkar, Kyung W Lee, Gordon Fishell, Fen Wang, Mitchell Goldfarb, Jean M Hébert
FGF signaling, an important component of intercellular communication, is required in many tissues throughout development to promote diverse cellular processes. Whether FGF receptors (FGFRs) accomplish such varied tasks in part by activating different intracellular transducers in different contexts remains unclear. Here we use the developing mouse telencephalon as an example to study the role of the FRS adapters, FRS2 and FRS3, in mediating the functions of FGFRs. Using tissue-specific and germline mutants, we examine the requirement of Frs genes in two FGFR-dependent processes...
May 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28481834/immunohistochemical-profiling-of-corneas-with-fuchs-endothelial-corneal-dystrophy
#11
An-Katrien De Roo, Thomas Janssens, Beatrijs Foets, Joost J van den Oord
PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is the leading indication for endothelial keratoplasty. Further insight into its pathophysiology is needed to develop alternative therapies. METHODS: Sixteen genes from a previous microarray expression experiment (FECD vs. normal) were validated using immunohistochemistry on paraffin-embedded corneas (n = 6 FECD, n = 6 normal). The results were quantified manually and semiautomatically. RESULTS: A higher percentage of corneal endothelial cells stained for alpha-smooth muscle actin (αSMA), cytokeratin 7, and superoxide dismutase 3 in FECD versus normal [odds ratios (ORs) of 60...
May 3, 2017: Cornea
https://www.readbyqxmd.com/read/28467822/fgf-dependent-metabolic-control-of-vascular-development
#12
Pengchun Yu, Kerstin Wilhelm, Alexandre Dubrac, Joe K Tung, Tiago C Alves, Jennifer S Fang, Yi Xie, Jie Zhu, Zehua Chen, Frederik De Smet, Jiasheng Zhang, Suk-Won Jin, Lele Sun, Hongye Sun, Richard G Kibbey, Karen K Hirschi, Nissim Hay, Peter Carmeliet, Thomas W Chittenden, Anne Eichmann, Michael Potente, Michael Simons
Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism, little is understood about the role of fibroblast growth factors (FGFs) in this context...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28466272/bfgf-protects-against-oxygen-glucose-deprivation-reoxygenation-induced-endothelial-monolayer-permeability-via-s1pr1-dependent-mechanisms
#13
Li Lin, Qingzhi Wang, Kenny Qian, Zeyuan Cao, Jian Xiao, Xiaoying Wang, Xiaokun Li, Zhanyang Yu
Blood-brain barrier (BBB) disruption is a common pathological feature of many neurological disorders including stroke and brain trauma, therefore is an important therapeutic target for treatment of these diseases. Basic fibroblast growth factor (bFGF) as a member of FGF superfamily plays critical roles in angiogenesis, neurogenesis, and neuron survival. We recently showed that recombinant bFGF protects against BBB disruption in traumatic brain injury in mice. In this study, we further investigated the mechanisms of recombinant bFGF in BBB protection by measuring the permeability of cultured endothelial cell monolayer induced by oxygen-glucose deprivation and reoxygenation (OGD/R)...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28465335/cdc42-is-required-for-epicardial-and-pro-epicardial-development-by-mediating-fgf-receptor-trafficking-to-the-plasma-membrane
#14
Jingjing Li, Lianjie Miao, Chen Zhao, Wasay Mohiuddin Shaikh Qureshi, David Shieh, Hua Guo, Yangyang Lu, Saiyang Hu, Alice Huang, Lu Zhang, Chen-Leng Cai, Leo Q Wan, Hongbo Xin, Peter Vincent, Harold A Singer, Yi Zheng, Ondine Cleaver, Zhen-Chuan Fan, Mingfu Wu
The epicardium contributes to multiple cardiac lineages and is essential for cardiac development and regeneration. However, the mechanism of epicardium formation is unclear. This study aimed to establish the cellular and molecular mechanisms underlying the dissociation of pro-epicardial cells (PECs) from the pro-epicardium (PE) and their subsequent translocation to the heart to form the epicardium. We used lineage tracing, conditional deletion, mosaic analysis and ligand stimulation in mice to determine that both villous protrusions and floating cysts contribute to PEC translocation to myocardium in a CDC42-dependent manner...
May 1, 2017: Development
https://www.readbyqxmd.com/read/28463984/%C3%AE-klotho-expression-determines-nitric-oxide-synthesis-in-response-to-fgf-23-in-human-aortic-endothelial-cells
#15
Chih-Ping Chung, Yu-Chun Chang, Yan Ding, Kenneth Lim, Qinghua Liu, Langjing Zhu, Wei Zhang, Tzong-Shi Lu, Guerman Molostvov, Daniel Zehnder, Li-Li Hsiao
Endothelial cells (ECs) express fibroblast growth factor (FGF) receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot...
2017: PloS One
https://www.readbyqxmd.com/read/28452589/lysyl-oxidase-propeptide-promotes-adipogenesis-through-inhibition-of-fgf-2-signaling
#16
John D Griner, Carl J Rogers, Mei-Jun Zhu, Min Du
Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine residues in collagen and elastin, key components of connective tissue. LOX is synthesized as an inactive 50 kD pre-proenzyme, and secreted to the extracellular matrix where it is cleaved into an active 32 kD LOX, and an 18kD free propeptide (LOX-PP), purportedly an inhibitor of fibroblast growth factor-2 (FGF-2) signaling. Given that adipocytes are distributed inside the connective tissue, it is likely that LOX-PP has an important regulatory role in adipogenesis, which has not been studied...
January 2, 2017: Adipocyte
https://www.readbyqxmd.com/read/28451171/antiangiogenic-platinum-through-glycan-targeting
#17
Erica J Peterson, A Gerard Daniel, Samantha J Katner, Lisa Bohlmann, Chih-Wei Chang, Anna Bezos, Christopher R Parish, Mark von Itzstein, Susan J Berners-Price, Nicholas P Farrell
Heparan sulfate is identified as a ligand receptor for polynuclear platinum anti-cancer agents through sulfate cluster binding. We present a new biological role for platinum and coordination compounds and a new target for metal-based drugs while presenting a new chemotype for heparanase and growth factor inhibition through modulation (metalloshielding) of their interactions. Masking of extracellular (ECM)-resident heparan sulfate (HS) through metalloshielding results in very effective inhibition of physiologically critical HS functions including enzyme (heparanase, HPSE) and protein growth factor recognition...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28445992/interaction-between-the-estrogen-receptor-and-fibroblast-growth-factor-receptor-pathways-in-non-small-cell-lung-cancer
#18
Jill M Siegfried, Mariya Farooqui, Natalie J Rothenberger, Sanja Dacic, Laura P Stabile
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#19
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28441778/gene-expression-analysis-before-and-after-treatment-with-adalimumab-in-patients-with-ankylosing-spondylitis-identifies-molecular-pathways-associated-with-response-to-therapy
#20
Marzia Dolcino, Elisa Tinazzi, Andrea Pelosi, Giuseppe Patuzzo, Francesca Moretta, Claudio Lunardi, Antonio Puccetti
The etiology of Ankylosing spondylitis (AS) is still unknown and the identification of the involved molecular pathogenetic pathways is a current challenge in the study of the disease. Adalimumab (ADA), an anti-tumor necrosis factor (TNF)-alpha agent, is used in the treatment of AS. We aimed at identifying pathogenetic pathways modified by ADA in patients with a good response to the treatment. Gene expression analysis of Peripheral Blood Cells (PBC) from six responders and four not responder patients was performed before and after treatment...
April 24, 2017: Genes
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