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FGF Receptor

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https://www.readbyqxmd.com/read/28819302/generation-and-intracellular-trafficking-of-a-polysialic-acid-carrying-fragment-of-the-neural-cell-adhesion-molecule-ncam-to-the-cell-nucleus
#1
Nina Westphal, Gabriele Loers, David Lutz, Thomas Theis, Ralf Kleene, Melitta Schachner
Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818669/notch-and-fgf-signaling-during-electrosensory-versus-mechanosensory-lateral-line-organ-development-in-a-non-teleost-ray-finned-fish
#2
Melinda S Modrell, Olivia R A Tidswell, Clare V H Baker
The lateral line system is a useful model for studying the embryonic and evolutionary diversification of different organs and cell types. In jawed vertebrates, this ancestrally comprises lines of mechanosensory neuromasts over the head and trunk, flanked on the head by fields of electrosensory ampullary organs, all innervated by lateral line neurons in cranial lateral line ganglia. Both types of sense organs, and their afferent neurons, develop from cranial lateral line placodes. Current research primarily focuses on the posterior lateral line primordium in zebrafish, which migrates as a cell collective along the trunk; epithelial rosettes form in the trailing zone and are deposited as a line of neuromasts, within which hair cells and supporting cells differentiate...
August 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28815598/lpa1-is-a-key-mediator-of-intracellular-signalling-and-neuroprotection-triggered-by-tetracyclic-antidepressants-in-hippocampal-neurons
#3
Maria C Olianas, Simona Dedoni, Pierluigi Onali
Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In the present study we examined the role of LPA receptors in the regulation of ERK1/2 activity and neuronal survival by the tetracyclic antidepressants mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells antidepressants and LPA induced a time- and concentration-dependent stimulation of ERK1/2 phosphorylation...
August 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28813681/uncoupling-the-mitogenic-and-metabolic-functions-of-fgf1-by-tuning-fgf1-fgf-receptor-dimer-stability
#4
Zhifeng Huang, Yi Tan, Junlian Gu, Yang Liu, Lintao Song, Jianlou Niu, Longwei Zhao, Lakshmi Srinivasan, Qian Lin, Jingjing Deng, Yang Li, Daniel J Conklin, Thomas A Neubert, Lu Cai, Xiaokun Li, Moosa Mohammadi
The recent discovery of metabolic roles for fibroblast growth factor 1 (FGF1) in glucose homeostasis has expanded the functions of this classically known mitogen. To dissect the molecular basis for this functional pleiotropy, we engineered an FGF1 partial agonist carrying triple mutations (FGF1(ΔHBS)) that diminished its ability to induce heparan sulfate (HS)-assisted FGF receptor (FGFR) dimerization and activation. FGF1(ΔHBS) exhibited a severely reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1 in vitro and in vivo...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#5
Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28805978/obeticholic-acid-a-selective-farnesoid-x-receptor-agonist-regulates-bile-acid-homeostasis-in-sandwich-cultured-human-hepatocytes
#6
Yuanyuan Zhang, Jonathan P Jackson, Robert L St Claire, Kimberly Freeman, Kenneth R Brouwer, Jeffrey E Edwards
Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28804438/green-tea-extract-induces-genes-related-to-browning-of-white-adipose-tissue-and-limits-weight-gain-in-high-energy-diet-fed-rat
#7
Li-Han Chen, Yi-Wen Chien, Chung-Tiang Liang, Ching-Hung Chan, Meng-Han Fan, Hui-Yu Huang
Background: A wealth of research has reported on the anti-obesity effects of green tea extract (GTE). Although browning of white adipose tissue (WAT) has been reported to attenuate obesity, no study has disclosed the effects of GTE on browning in Sprague Dawley rats. Objectives: The aims of the study were to investigate the effects of GTE on anti-obesity and browning, and their underlying mechanisms. Methods: Four groups of rats (n=10/group) were used including a normal diet with vehicle treatment, and a high-energy diet (HED) with vehicle or GTE by oral gavage at 77...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28791365/fgf8-promotes-cell-proliferation-and-resistance-to-egfr-inhibitors-via-upregulation-of-egfr-in-human-hepatocellular-carcinoma-cells
#8
Yuanmin Pei, Xueling Sun, Xiwei Guo, Huashan Yin, Le Wang, Fugu Tian, Hongxi Jing, Xiaobo Liang, Jun Xu, Pengcheng Shi
Fibroblast growth factor 8 (FGF8), a member of the fibroblast growth factor (FGF) family, is upregulated in several human cancers, including HCC (HCC). Previous studies have demonstrated that FGF8 increased cell growth and invasion of tumor cells. In the present study we investigated whether FGF8 is involved in the cell proliferation and resistance to several drugs in human HCC cells. We stably overexpressed FGF8 by lentiviral transfection. In addition, we also added recombinant FGF8 instead of stably overexpressing FGF8 in human HCC cells...
August 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28768168/what-s-so-special-about-fgf19-unique-effects-reported-on-skeletal-muscle-mass-and-function
#9
David J Glass
In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective.
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28757146/regulation-of-receptor-binding-specificity-of-fgf9-by-an-autoinhibitory-homodimerization
#10
Yang Liu, Jinghong Ma, Andrew Beenken, Lakshmi Srinivasan, Anna V Eliseenkova, Moosa Mohammadi
The epithelial fibroblast growth factor 9 (FGF9) subfamily specifically binds and activates the mesenchymal "c" splice isoform of FGF receptors 1-3 (FGFR1-3) to regulate organogenesis and tissue homeostasis. The unique N and C termini of FGF9 subfamily ligands mediate a reversible homodimerization that occludes major receptor binding sites within the ligand core region. Here we provide compelling X-ray crystallographic, biophysical, and biochemical data showing that homodimerization controls receptor binding specificity of the FGF9 subfamily by keeping the concentration of active FGF9 monomers at a level, which is sufficient for a normal FGFR "c" isoform binding/signaling, but is insufficient for an illegitimate FGFR "b" isoform binding/signaling...
July 11, 2017: Structure
https://www.readbyqxmd.com/read/28756207/pregnane-x-receptor-pxr-deficiency-improves-high-fat-diet-induced-obesity-via-induction-of-fibroblast-growth-factor-15-fgf15-expression
#11
Li-Yang Zhao, Jia-Yi Xu, Zhe Shi, Neal A Englert, Shu-Yun Zhang
Obesity has become a significant global health problem, and is a high risk factor for a variety of metabolic diseases. Fibroblast growth factor (FGF) 15 plays an important role in the regulation of metabolism. Xenobiotic-sensing nuclear receptors pregnane X receptor (PXR/NR1I2) and constitutive androstane receptor (CAR/NR1I3) play important roles in xenobiotic detoxification and metabolism, and also are involved in the regulation of energy metabolism. However, the effects that PXR and CAR have on the regulation of FGF15 are unknown...
July 26, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28738356/thermal-preconditioning-may-prevent-tendon-adhesion-by-up-regulating-hsp72-in-rats
#12
Yang Tan, Qin-Fen Wu, Qiang Wu, Xin-Ti Tan, Liao-Bin Chen, Xin Wang
BACKGROUND/AIMS: The study aims to determine the effects of thermal preconditioning on tendon adhesion by regulating the expression of heat shock protein 72 (HSP72) in rat models. METHODS: Sixty male Wistar rats were collected and randomly assigned into the thermal preconditioning and control groups. During the 4th and 8th weeks following surgery, 15 rats were sacrificed in each period respectively, and their tendon adhesion was observed and evaluated. Biomechanical testing was performed to measure the tensile strength and gliding distance of tendons...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28736761/phase-ii-study-of-dovitinib-in-patients-progressing-on-anti-vascular-endothelial-growth-factor-therapy
#13
Thomas J Semrad, Edward J Kim, Michael S Tanaka, Jacob Sands, Chris Roberts, Rebekah A Burich, Yu Li, David R Gandara, Primo Lara, Philip C Mack
BACKGROUND: Prior work identified the fibroblast growth factor (FGF) pathway as a mediator of resistance to anti-vascular endothelial growth factor (VEGF) therapy. We tested dovitinib, an inhibitor of both FGF and VEGF receptors, in patients progressing on anti-VEGF treatment. METHODS: Patients with measurable advanced colorectal or non-small cell lung cancer with progression despite anti-VEGF treatment within 56 days, good performance status and adequate organ function were eligible...
2017: Cancer Treat Res Commun
https://www.readbyqxmd.com/read/28735624/the-effect-of-prostaglandin-e2-receptor-ptger2-activation-on-growth-factor-expression-and-cell-proliferation-in-bovine-endometrial-explants
#14
Shuangyi Zhang, Bo Liu, Wei Mao, Qianru Li, Changqi Fu, Nan Zhang, Ying Zhang, Long Gao, Yuan Shen, Jinshan Cao
The domestic animal endometrium undergoes regular periods of regeneration and degeneration during cycles of oestrus and dioestrus. If blastocyst implantation occurs in the uterus, the endometrium will prepare for pregnancy by changing its pattern of development to build a connection with the embryo to nourish it. Prostaglandin E2 (PGE2) secretion synchronized with endometrial growth in these processes and could be involved in endometrial growth. One of the PGE2 receptors (PTGER2) is present in endometrium and its increased expression accompanies with endometrial growth in above processes...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28733346/regulation-and-action-of-early-growth-response-1-in-bovine-granulosa-cells
#15
Peng Han, Hilda Guerrero-Netro, Anthony Estienne, Binyun Cao, Christopher Price
Fibroblast growth factors (FGF) modify cell proliferation and differentiation through receptor tyrosine kinases, which stimulate the expression of transcription factors including members of the early growth response (EGR) family. In ovarian granulosa cells, most FGFs activate typical response genes, although the role of EGR proteins has not been described. In the present study, we determined the regulation of EGR mRNA by FGFs and explored the role of EGR1 in the regulation of FGF response genes. Addition of FGF1, FGF2, FGF4 or FGF8b increased EGR1 and EGR3 mRNA levels, whereas FGF18 increased only EGR1 mRNA abundance...
July 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28732181/irf6-and-spry4-signaling-interact-in-periderm-development
#16
Y A Kousa, R Roushangar, N Patel, A Walter, P Marangoni, R Krumlauf, O D Klein, B C Schutte
Rare mutations in IRF6 and GRHL3 cause Van der Woude syndrome, an autosomal dominant orofacial clefting disorder. Common variants in IRF6 and GRHL3 also contribute risk for isolated orofacial clefting. Similarly, variants within genes that encode receptor tyrosine kinase (RTK) signaling components, including members of the FGF pathway, EPHA3 and SPRY2, also contribute risk for isolated orofacial clefting. In the mouse, loss of Irf6 or perturbation of Fgf signaling leads to abnormal oral epithelial adhesions and cleft palate...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28730625/fgf9-mutation-causes-craniosynostosis-along-with-multiple-synostoses
#17
Maria Rodriguez-Zabala, Miriam Aza-Carmona, Carlos I Rivera-Pedroza, Alberta Belinchón, Isabel Guerrero-Zapata, Jimena Barraza-García, Elena Vallespin, Min Lu, Angela Del Pozo, Marc J Glucksman, Fernando Santos-Simarro, Karen E Heath
Craniosynostosis is commonly caused by mutations in fibroblast growth factor receptors (FGFRs), highlighting the essential role of FGF-mediated signaling in skeletal development. We set out to identify the molecular defect in a family referred for craniosynostosis and in whom no mutation was previously detected. Using next-generation sequencing, we identified a novel missense mutation in FGF9. Modeling based upon the crystal structure and functional studies confirmed its pathogenicity showing that it impaired homodimerization and FGFR3 binding...
July 21, 2017: Human Mutation
https://www.readbyqxmd.com/read/28729349/fgf9-prevents-pleural-fibrosis-induced-by-intra-pleural-adenovirus-injection-in-mice
#18
Aurélien Justet, Audrey Joannes, Valérie Besnard, Joëlle Marchal-Sommé, Madeleine Jaillet, Phillippe Bonniaud, Jean-Michel Sallenave, Brigitte Solhonne, Yves Castier, Pierre Mordant, Hervé Mal, Aurélie Cazes, Raphael Borie, Arnaud A Mailleux, Bruno Crestani
Fibroblast Growth Factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both Human and mouse lungs. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (Adcont) was performed...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28721153/fibroblast-growth-factor-23-iron-and-inflammation-are-they-related-in-early-stages-of-chronic-kidney-disease
#19
Ewelina Lukaszyk, Mateusz Lukaszyk, Ewa Koc-Zorawska, Anna Bodzenta-Lukaszyk, Jolanta Malyszko
INTRODUCTION: Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). MATERIAL AND METHODS: The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28718374/cancer-associated-fibroblasts-secrete-fgf-1-to-promote-ovarian-proliferation-migration-and-invasion-through-the-activation-of-fgf-1-fgfr4-signaling
#20
Yuanzhen Sun, Xiaoli Fan, Qing Zhang, Xiaoyu Shi, Guangwei Xu, Cuimin Zou
Ovarian cancer is the most lethal gynecologic malignancy, due to its high propensity for metastasis. Cancer-associated fibroblasts, as the dominant component of tumor microenvironment, are crucial for tumor progression. However, the mechanisms underlying the regulation of ovarian cancer cells by cancer-associated fibroblasts remain little known. Here, we first isolated cancer-associated fibroblasts from patients' ovarian tissues and found that cancer-associated fibroblasts promoted SKOV3 cells' proliferation, migration, and invasion...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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