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fibroblast growth factor receptor

Mercedes Tomé, Jan Tchorz, Martin Gassmann, Bernhard Bettler
Notch signalling regulates neural stem cell (NSC) proliferation, differentiation and survival for the correct development and functioning of the central nervous system. Overactive Notch2 signalling has been associated with poor prognosis of aggressive brain tumours, such as glioblastoma multiforme (GBM). We recently reported that constitutive expression of the Notch2 intracellular domain (N2ICD) enhances proliferation and gliogenesis in NSCs. Here, we investigated the mechanism by which Notch2 promotes resistance to apoptosis of NSCs to cytotoxic insults...
February 7, 2019: Stem Cell Research
Lianne de Haan, Sarah J van der Lely, Anne-Loes K Warps, Quincy Hofsink, Pim B Olthof, Mark J de Keijzer, Daniël A Lionarons, Lionel Mendes-Dias, Bote G Bruinsma, Korkut Uygun, Hartmut Jaeschke, Geoffrey C Farrell, Narci Teoh, Rowan F van Golen, Tiangang Li, Michal Heger
Background: Liver regeneration following partial hepatectomy (PHx) is a complicated process involving multiple organs and several types of signaling networks. The bile acid-activated metabolic pathways occupy an auxiliary yet important chapter in the entire biochemical story. PHx is characterized by rapid but transient bile acid overload in the liver, which constitutes the first wave of proliferative signaling in the remnant hepatocytes. Bile acids trigger hepatocyte proliferation through activation of several nuclear receptors...
May 28, 2018: Journal of Clinical and Translational Research
Cong Wang, Ziying Liu, Yuepeng Ke, Fen Wang
Advanced castrate-resistant prostate cancer (CRPC) is a poorly prognostic disease currently lacking effective cure. Understanding the molecular mechanism that underlies the initiation and progression of CRPC will provide new strategies for treating this deadly disease. One candidate target is the fibroblast growth factor (FGF) signaling axis. Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions...
2019: Frontiers in Genetics
Subhendu Mukherjee, Wei Sheng, Alexander Michkov, Krishna Sriarm, Rui Sun, Anna Dvorkin-Gheva, Paul A Insel, Luke J Janssen
We have shown that calcium (Ca2+ ) oscillations in human pulmonary fibroblasts (HPFs) contribute to pro-fibrotic effects of TGFβ and that disruption of these oscillations blunts features of pulmonary fibrosis. Prostaglandin E2 (PGE2 ) exerts anti-fibrotic effects in the lung but the mechanisms for this action are not well defined. We thus sought to explore interactions between PGE2 and the pro-fibrotic agent transforming growth factor beta (TGFβ) in pulmonary fibroblasts (PFs) isolated from patients with or without idiopathic pulmonary fibrosis (IPF)...
February 13, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Miyuki Yokoi, Koh-Ichi Kuremoto, Shinsuke Okada, Miwa Sasaki, Kazuhiro Tsuga
Attenuation of fibroblast growth factor receptor (FGFR) 2b signaling suppresses the differentiation of oral epithelial stem cells to ameloblasts, their survival and viability remaining unaffected; however, its effect on dentin formation is unknown. This study aimed to clarify the effect of attenuation of FGFR2b signaling on odontoblast differentiation and dentin formation. Initially, we used a murine rtTA transactivator/tetracycline promoter system for inducible and reversible attenuation of FGFR2b signaling in adult mice...
February 12, 2019: In Vitro Cellular & Developmental Biology. Animal
Isabel S Jerchel, Alex Q Hoogkamer, Ingrid M Ariës, Judith M Boer, Nicolle J M Besselink, Marco J Koudijs, Rob Pieters, Monique L den Boer
The FGF receptor signaling pathway is recurrently involved in the leukemogenic processes. Oncogenic fusions of FGFR1 with various fusion partners were described in myeloid proliferative neoplasms, and overexpression and mutations of FGFR3 are common in multiple myeloma. In addition, fibroblast growth factors are abundant in the bone marrow, and they were shown to enhance the survival of acute myeloid leukemia cells. Here we investigate the effect of FGFR stimulation on pediatric BCP-ALL cells in vitro, and search for mutations with deep targeted next-generation sequencing of mutational hotspots in FGFR1, FGFR2, and FGFR3...
February 12, 2019: Scientific Reports
Emma Bränn, Åsa Edvinsson, Anna Rostedt Punga, Inger Sundström-Poromaa, Alkistis Skalkidou
During pregnancy, the woman's body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period...
February 12, 2019: Scientific Reports
Quang T Nguyen, Mohamed Jalloul Nsaibia, Martin G Sirois, Angelino Calderone, Jean-Claude Tardif, Yan Fen Shi, Matthieu Ruiz, Caroline Daneault, Lyne Gagnon, Brigitte Grouix, Pierre Laurin, Jocelyn Dupuis
Aims: Heart failure with reduced ejection fraction (HFrEF) causes lung remodelling with myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome with pulmonary hypertension (PH) and right ventricular (RV) dysfunction. PBI-4050 is a first-in-class anti-fibrotic, anti-inflammatory and anti-proliferative compound. The present study evaluated the therapeutic impact of PBI-4050 on PH in an HFrEF model. Methods and Results: HFrEF was induced after myocardial infarction (MI) in rats...
February 7, 2019: Cardiovascular Research
Vishal J Patel, Amit A Joharapurkar, Samadhan G Kshirsagar, Brijesh K Sutariya, Maulik S Patel, Rajesh H Bahekar, Mukul R Jain
BACKGROUND: Balanced coagonists of glucagon-like peptide-1 (GLP-1) and glucagon receptors are emerging therapies for the treatment of obesity and diabetes. Such coagonists also regulate lipid metabolism, independent of their body weight lowering effects. Many actions of the coagonists are partly mediated by fibroblast growth factor 21 (FGF21) signaling, with the major exception of bile homeostasis. Since thyroid hormone is an important regulator of bile homeostasis, we studied the involvement of thyroid hormone in coagonist-induced changes in lipid and bile metabolism...
February 11, 2019: Current Molecular Pharmacology
Martin H Voss, Cinta Hierro, Rebecca S Heist, James M Cleary, Funda Meric-Bernstam, Josep Tabernero, Filip Janku, Leena Gandhi, A John Iafrate, Darrell R Borger, Nobuya Ishii, Youyou Hu, Yulia Kirpicheva, Valerie Nicolas-Metral, Anna Pokorska-Bocci, Anne Vaslin Chessex, Claudio Zanna, Keith T Flaherty, José Baselga
PURPOSE: To investigate tolerability, efficacy, and pharmacokinetics/-dynamics (PK/PD) of Debio 1347, a selective fibroblast growth factor receptor (FGFR) Inhibitor. EXPERIMENTAL DESIGN: This was a first-in-human, multicenter, open-label study in patients with advanced solid tumors harboring FGFR1-3 gene alterations. Eligible patients received oral Debio 1347 at escalating doses once daily until disease progression or intolerable toxicity. Dose limiting toxicities (DLTs) were evaluated during the first 4 weeks on treatment, PK/PD post-first dose and after 4 weeks...
February 11, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Cassandra Ringuette Goulet, Audrey Champagne, Geneviève Bernard, Dominique Vandal, Stéphane Chabaud, Frédéric Pouliot, Stéphane Bolduc
BACKGROUND: Cancer-associated fibroblasts (CAFs), activated by tumour cells, are the predominant type of stromal cells in cancer tissue and play an important role in interacting with neoplastic cells to promote cancer progression. Epithelial-mesenchymal transition (EMT) is a key feature of metastatic cells. However, the mechanism by which CAFs induce EMT program in bladder cancer cells remains unclear. METHODS: To investigate the role of CAFs in bladder cancer progression, healthy primary bladder fibroblasts (HFs) were induced into CAFs (iCAFs) by bladder cancer-derived exosomes...
February 11, 2019: BMC Cancer
Rabjot Rai, Joe Iwanaga, Graham Dupont, Rod J Oskouian, Marios Loukas, W Jerry Oakes, R Shane Tubbs
INTRODUCTION: Pfeiffer syndrome is a rare autosomal dominant inherited disorder associated with craniosynostosis, midfacial hypoplasia, and broad thumbs and toes. The syndrome has been divided into three clinical subtypes based on clinical findings. METHODS: This review will specifically examine the most severe type, Pfeiffer syndrome type 2, focusing on its genetics and molecular biology. CONCLUSION: This subtype of the syndrome is caused by de novo sporadic mutations, the majority of which occur in the fibroblast growth factor receptor type 1 and 2 (FGFR1/2) genes...
February 11, 2019: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Semra Koçtürk, Mehtap Yüksel Egrilmez, Şebnem Aktan, Gülgün Oktay, Halil Resmi, Hatice Şimşek Keskin, Belgin Sert Serdar, Tugba Erkmen, Gül Güner Akdogan, Şebnem Özkan
BACKGROUND: People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen-activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP-1 subunits in the nucleus which induce matrix metalloproteinases...
February 10, 2019: Photodermatology, Photoimmunology & Photomedicine
Geovanna O Pires, Itamar O Vieira, Fabiana R Hernandes, Andre L Teixeira, Ivone B Oliveira, Wagner V Dominguez, Luciene M Dos Reis, Fábio M Montenegro, Rosa M Moysés, Aluizio B Carvalho, Vanda Jorgetti
Secondary hyperparathyroidism is a complication of chronic kidney disease that compromises skeletal integrity. In patients with secondary hyperparathyroidism undergoing parathyroidectomy, parathyroid hormone levels dramatically decrease. The effects of parathyroidectomy on bone tissue are poorly understood, especially regarding the proteins expressed by osteocytes, such as fibroblast growth factor 23, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, sclerostin, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin, which regulate bone turnover...
February 6, 2019: Bone
Jia Wang, Wei Shen, Jun-Yan Zhang, Chang-Hao Jia, Mei-Lin Xie
Stevioside, a natural glycoside compound, has many beneficial biological activities, but its protective effect on myocardial fibrosis has not been reported yet. This study aimed to investigate the effect of stevioside. The isoproterenol-induced model mice were orally given stevioside 75-300 mg kg-1 for 40 days. The results showed that after the administration of stevioside, the myocardial hydroxyproline, collagen accumulation, and protein expressions of collagen I/III, α-smooth muscle actin, transforming growth factor-β1 (TGF-β1), nuclear factor kappa B p65 (NF-κB p65), Smad2/3, and P-Smad2/3 were decreased, while the glutathione peroxidase and superoxide dismutase levels in serum and myocardial tissues and protein expressions of myocardial peroxisome proliferator-activated receptor γ (PPARγ) and Smad7 were increased...
February 8, 2019: Food & Function
Erika Terzuoli, Ginevra Nannelli, Antonio Giachetti, Lucia Morbidelli, Marina Ziche, Sandra Donnini
PURPOSE: Endothelial-to-mesenchymal transition (EndMT) plays an important role in pathogenesis of a number of inflammatory diseases. Hydroxytyrosol (HT) and, particularly, its major plasma metabolite HT-3O sulfate (HT-3Os) are known olive oil antioxidant and anti-inflammatory polyphenols which exert benefits against vascular diseases by improving endothelial function. However, to date the HT-3Os role in EndMT is not well known. METHODS: To investigate the HT-3Os effects on EndMT in the inflamed endothelium, we used an in vitro model of endothelial dysfunction, challenging endothelial cells (EC), human umbilical EC (HUVEC) and human retinal EC (HREC) with Interleukin-1β (IL-1β), an inflammatory agent...
February 6, 2019: European Journal of Nutrition
Bong Kyun Park, Chang Won Kim, Jeong Eun Kwon, Manorma Negi, Yong Tae Koo, Sang Hun Lee, Dong Hyun Baek, Yoo Hun Noh, Se Chan Kang
CONTEXT: Lespedeza cuneata G. Don (Fabaceae), has been used as a traditional treatment of various diseases. There is a report L. cuneata effects on hormone replacement therapy for endocrine-related disease. However, studies related to benign prostatic hyperplasia (BPH) have not been investigated. OBJECTIVE: The effects of L. cuneata aqueous extract (LCW) on testosterone-induced prostatic hyperplasia (TPH) were examined. MATERIALS AND METHODS: Male Wistar rats (10 weeks, 330-350 g) were randomly divided to 6 groups (n = 6): Control group; TPH group (3 mg/kg, s...
December 2019: Pharmaceutical Biology
Benjamin Schrijver, Merel Aafke Kooiman, Esmee Kasteleijn, Conny van Holten-Neelen, Sita Virakul, Dion Paridaens, Robin Peeters, P Martin van Hagen, Virgil Dalm, Willem A Dik
PURPOSE: Basic fibroblast growth factor (bFGF) has been implicated in the pathogenesis of Graves' orbitopathy (GO). It stimulates several processes, including hyaluronan synthesis, involved in orbital tissue volume expansion and may act synergistically with platelet derived growth factor (PDGF)-BB. PDGF-BB is known to stimulate adipogenesis in orbital fibroblasts, but the effect of bFGF on adipogenesis in orbital fibroblasts is so far unknown. This study was conducted to determine: 1) whether bFGF induces adipogenesis in orbital fibroblasts, 2) whether bFGF and PDGF-BB together exert an additive or synergistic effect on adipogenesis and 3) to study whether treatment directed at bFGF- and PDGF-BB signaling may potentially be of interest for the treatment of GO...
February 6, 2019: Thyroid: Official Journal of the American Thyroid Association
Jun Teishima, Tetsutaro Hayashi, Hirotaka Nagamatsu, Koichi Shoji, Hiroyuki Shikuma, Ryoken Yamanaka, Yohei Sekino, Keisuke Goto, Shogo Inoue, Akio Matsubara
Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) play an important role in the maintenance of tissue homeostasis and the development and differentiation of prostate tissue through epithelial-stromal interactions. Aberrations of this signaling are linked to the development and progression of prostate cancer (PCa). The FGF family includes two subfamilies, paracrine FGFs and endocrine FGFs. Paracrine FGFs directly bind the extracellular domain of FGFRs and act as a growth factor through the activation of tyrosine kinase signaling...
February 4, 2019: Journal of Clinical Medicine
Nathalie Javidi-Sharifi, Jacqueline Martinez, Isabel English, Sunil K Joshi, Renata Scopim-Ribiero, David K Edwards, Anupriya Agarwal, Claudia Lopez, Danielle Jorgens, Jeffrey W Tyner, Brian J Druker, Elie Traer
Protective signaling from the leukemia microenvironment leads to leukemia cell persistence, development of resistance, and disease relapse. Here, we demonstrate that fibroblast growth factor 2 (FGF2) from bone marrow stromal cells is secreted in exosomes, which are subsequently endocytosed by leukemia cells, and protect leukemia cells from tyrosine kinase inhibitors (TKIs). Expression of FGF2 and its receptor, FGFR1, are both increased in a subset of stromal cell lines and primary AML stroma; and increased FGF2/FGFR1 signaling is associated with increased exosome secretion...
February 5, 2019: ELife
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