DOCSLIB.ORG

TABLE S1 Complete Overview of Protocols for Induction of Pscs Into

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
TABLE S1 Complete Overview of Protocols for Induction of Pscs Into TABLE S1 Complete overview of protocols for induction of PSCs into renal lineages Ref 2D/ Cell type Protocol Days Growth factors Outcome Other analyses # 3D hiPSC, hESC, Collagen type I tx murine epidydymal fat pads,ex vivo 54 2D 8 Y27632, AA, CHIR, BMP7 IM miPSC, mESC Matrigel with murine fetal kidney hiPSC, hESC, Suspension,han tx murine epidydymal fat pads,ex vivo 54 2D 20 AA, CHIR, BMP7 IM miPSC, mESC ging drop with murine fetal kidney tx murine epidydymal fat pads,ex vivo 55 hiPSC, hESC Matrigel 2D 14 CHIR, TTNPB/AM580, Y27632 IM with murine fetal kidney Injury, tx murine epidydymal fat 57 hiPSC Suspension 2D 28 AA, CHIR, BMP7, TGF-β1, TTNPB, DMH1 NP pads,spinal cord assay Matrigel,membr 58 mNPC, hESC 3D 7 BPM7, FGF9, Heparin, Y27632, CHIR, LDN, BMP4, IGF1, IGF2 NP Clonal expansion ane filter iMatrix,spinal 59 hiPSC 3D 10 LIF, Y27632, FGF2/FGF9, TGF-α, DAPT, CHIR, BMP7 NP Clonal expansion cord assay iMatrix,spinal 59 murine NP 3D 8-19 LIF, Y27632, FGF2/FGF9, TGF- α, DAPT, CHIR, BMP7 NP Clonal expansion cord assay murine NP, Suspension, 60 3D 7-19 BMP7, FGF2, Heparin, Y27632, LIF NP Nephrotoxicity, injury model human NP membrane filter Suspension, Contractility and permeability assay, ex 61 hiPSC 2D 10 AA, BMP7, RA Pod gelatin vivo with murine fetal kidney Matrigel. 62 hiPSC, hESC fibronectin, 2D < 50 FGF2, AA, WNT3A, BMP4, BMP7, RA, FGF2, HGF or RA + VITD3 Pod collagen type I Matrigel, Contractility and uptake assay,ex vivo 63 hiPSC 2D 13 Y27632, CP21R7, BMP4, RA, BMP7, FGF9, VITD3 Pod collagen type I with murine fetal kidney Collagen production, clearance studies, 64 hiPSC Laminin-511 2D 21 AA, CHIR, Y27632, BMP7, VEGF, RA Pod injury model Transporter and GGT 65 hiPSC Matrigel 2D 8 Y27632, BMP2, BMP7 PT activity,nephrotoxicity tx under murine skin,ex vivo into murine 66 hESC Matrigel 2D 20 AA, RA, BMP2, BMP7 PT kidney cortex tx murine kidney capsule,ex vivo with 67 hiPSC, hESC Geltrex 2D 11-12 Y27632, CHIR, FGF2, RA PT,MM murine fetal kidney tx murine kidney capsule,ex vivo with 67 hiPSC, hESC Geltrex 2D 8 Y27632, CHIR, FGF2, RA, FGF9, AA PT,MM murine fetal kidney 69 hiPSC, hESC Matrigel 2D 4 BMP4, FGF2, RA, AA, BMP2, Y27632 UB ex vivo with murine fetal kidney Matrigel, 2D, LDN, A83-01, CHIR, RA, PD0325901, FGF8, TTNPB, A83-01, GDNF, 70 hiPSC, hESC 15 UB suspension 3D FGF1, Thiazovin Suspension, UB: Y27632(iPSC), AA, BMP4, CHIR, RA, FGF9, LDN(iPSC), 71 hiPSC membrane 3D 7 UB, MM Spinal cord assay SB431542 (iPSC), FGF1, GDNF, Rspondin1, FGF7(iPSC) filter,matrigel NP: LIF (ESC), PD0325901 (ESC), Y27632, AA, bFGF(iPSC), CHIR, 71 BMP4, RA, LDN(iPSC), BMS493(iPSC), FGF9 UB, MM Spinal cord assay Suspension, LIF, CHIR, PD0325901, AA, Y27632, AA, BMP4, CHIR, RA, 71 mESC membrane 3D 7 UB,MM tx murine kidney capsule Y27632, FGF9 (mESC-derived NPs) filter,matrigel Matrigel PT, pod, Permeability and toxicity assay,disease 73 hiPSC, hESC 3D 16 Y27632, CHIR, B27 sandwich endo modeling, tx in murine kidney 74 hESC Matrigel. 3D 18-22 BMP4, AA, CHIR, RA, FGF9, heparin UB,MM ex vivo with murine fetal kidney membrane filter MM, UB, Matrigel, 2D, 10 hiPSC, hESC 12-25 CHIR, FGF9 endo, Endocytosis, nephrotoxicity membrane filter 3D stroma 76 MEK Membrane filter 3D 5 Condensate with amniotic fluid stem cells Pod tx murine kidney capsule Pod, PT, 77 MEK Matrigel 3D 1-4 Condensate with MSC and HUVECs Intracranial tx DT Suspension, 2D, UB and 78 hiPSC 14-90 Y27632, CHIR, Noggin/ Dorsomorphin, AA, FGF9 Nephrotoxicity Geltrex 3D MM Suspension, 2D, 79 hiPSC, hESC 21-28 CHIR, Noggin, AA, FGF9 MM Nephrotoxicity Geltrex 3D MM, 80 hiPSC, hESC Geltrex 3D 14-21 CHIR, VEGF165, FGF9, Y27632, AA, BMP4, bFGF endo, Nephrotoxicity, disease modeling stroma hiPSC, hESC, 8,5- Pod, PT, Injury model,tx omentum and chick 81 Membrane filter 3D AA, BMP4, CHIR, RA, FGF2, FGF9 mESC 14 DT embryo coelomic cavity ESC, embryonic stem cell; iPSC, induced pluripotent stem cell; h-/m-, human/murine; NP, nephron progenitor; MEK, murine embryonic kidney; IM, intermediate mesoderm; NP, nephron progenitor; Pod, podocytes; PT, proximal tubuli; UB, ureteric bud; MM, metanephric mesenchyme; endo, endothelial cells; DT, distal tubuli; Tx, transplantation TABLE S2 Glossary A83-01, Activin/NODAL/TGF-β pathway ESC, embryonic stem cellESRD, end inhibitor stage renal disease AA, Activin A FGF, fibroblast growth factor AM580, Retinoic acid receptor (RAR) GDNF, glial cell-derived neurotrophic agonist factor ARPC, adult renal progenitor cell hESC, human ESC B27, serum-free supplement HGF, hepatocyte growth factor BMP, bone morphogenetic protein hiPSC, human iPSC BMS493, retinoid pathway activator IGF, insulin-like growth factor CHIR, CHIR99021, WNT activator IM, intermediate mesoderm CITED1, Cbp/p300-interacting iPSC, induced pluripotent stem cell transactivator 1 LDN, LDN193189 DAPT, Notch inhibitor LIF, leukemia inhibitory factor DT, distal tubuli mESC, murine ESC DMH1, selective BMP antagonist miPSC, murine iPSC EGF, epidermal growth factor mPSC, murine pluripotent stem cells Endo, endothelial cells MEK, murine embryonic kidney SIX2, homeobox protein SIX2 MM, metanephric mesenchyme SYN, synaptophysin MSC, Mesenchymal stem cell TGF, transforming growth factor NP, nephron progenitor TTNPB, Retinoic acid receptor (RAR) agonist OSR1, protein odd-skipped-related 1 Tx, transplantation PD0325901, MEK/ERK pathway inhibitor UB, ureteric bud PAX2, Paired box gene 2 VEGF, vascular endothelial growth factor PDGFR, Platelet-derived growth factor receptor VITD3, vitamin D3 PODOCAL, podocalcyn WD, Wolffian Duct Pod, podocytes Wnt3A, protein Wnt-3a PSC, pluripotent stem cell WT1, Wilms Tumor 1 PT, proximal tubuli Y27632, ROCK Inhibitor RA, retinoic acid SALL1, Spalt-like transcription factor 1 SB431542, Activin/BMP/TGF-β pathway inhibitor .
Load more

Recommended publications
  • Fgf17b and FGF18 Have Different Midbrain Regulatory Properties from Fgf8b Or Activated FGF Receptors Aimin Liu1,2, James Y
    Research article 6175 FGF17b and FGF18 have different midbrain regulatory properties from FGF8b or activated FGF receptors Aimin Liu1,2, James Y. H. Li2, Carrie Bromleigh2, Zhimin Lao2, Lee A. Niswander1 and Alexandra L. Joyner2,* 1Howard Hughes Medical Institute, Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA 2Howard Hughes Medical Institute and Skirball Institute of Biomolecular Medicine, Departments of Cell Biology, and Physiology and Neuroscience, NYU School of Medicine, New York, NY 10016, USA *Author for correspondence (e-mail: [email protected]) Accepted 28 August 2003 Development 130, 6175-6185 Published by The Company of Biologists 2003 doi:10.1242/dev.00845 Summary Early patterning of the vertebrate midbrain and region in the midbrain, correlating with cerebellum cerebellum is regulated by a mid/hindbrain organizer that development. By contrast, FGF17b and FGF18 mimic produces three fibroblast growth factors (FGF8, FGF17 FGF8a by causing expansion of the midbrain and and FGF18). The mechanism by which each FGF upregulating midbrain gene expression. This result is contributes to patterning the midbrain, and induces a consistent with Fgf17 and Fgf18 being expressed in the cerebellum in rhombomere 1 (r1) is not clear. We and midbrain and not just in r1 as Fgf8 is. Third, analysis of others have found that FGF8b can transform the midbrain gene expression in mouse brain explants with beads soaked into a cerebellum fate, whereas FGF8a can promote in FGF8b or FGF17b showed that the distinct activities of midbrain development. In this study we used a chick FGF17b and FGF8b are not due to differences in the electroporation assay and in vitro mouse brain explant amount of FGF17b protein produced in vivo.
    [Show full text]
  • Fgf8 Is Mutated in Zebrafish Acerebellar
    Development 125, 2381-2395 (1998) 2381 Printed in Great Britain © The Company of Biologists Limited 1998 DEV1265 Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis Frank Reifers1, Heike Böhli1, Emily C. Walsh2, Phillip H. Crossley2, Didier Y. R. Stainier2 and Michael Brand1,* 1Department of Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany 2Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143-0554, USA *Author for correspondence (e-mail: [email protected]) Accepted 2 April; published on WWW 3 June 1998 SUMMARY We describe the isolation of zebrafish Fgf8 and its gastrulation, and that Fgf8 functions later during expression during gastrulation, somitogenesis, fin bud and somitogenesis to polarize the midbrain. Fgf8 is also early brain development. By demonstrating genetic linkage expressed in a dorsoventral gradient during gastrulation and by analysing the structure of the Fgf8 gene, we show and ectopically expressed Fgf8 can dorsalize embryos. that acerebellar is a zebrafish Fgf8 mutation that may Nevertheless, acerebellar mutants show only mild inactivate Fgf8 function. Homozygous acerebellar embryos dorsoventral patterning defects. Also, in spite of the lack a cerebellum and the midbrain-hindbrain boundary prominent role suggested for Fgf8 in limb development, the organizer. Fgf8 function is required to maintain, but not pectoral fins are largely unaffected in the mutants. Fgf8 is initiate, expression of Pax2.1 and other marker genes in this therefore required in development of several important area. We show that Fgf8 and Pax2.1 are activated in signaling centers in the zebrafish embryo, but may be adjacent domains that only later become overlapping, and redundant or dispensable for others.
    [Show full text]
  • Different Fgfs Have Distinct Roles in Regulating Neurogenesis After Spinal Cord Injury in Zebrafish Yona Goldshmit1,2, Jean Kitty K
    Goldshmit et al. Neural Development (2018) 13:24 https://doi.org/10.1186/s13064-018-0122-9 RESEARCHARTICLE Open Access Different Fgfs have distinct roles in regulating neurogenesis after spinal cord injury in zebrafish Yona Goldshmit1,2, Jean Kitty K. Y. Tang1, Ashley L. Siegel1, Phong D. Nguyen1, Jan Kaslin1, Peter D. Currie1 and Patricia R. Jusuf1,3* Abstract Background: Despite conserved developmental processes and organization of the vertebrate central nervous system, only some vertebrates including zebrafish can efficiently regenerate neural damage including after spinal cord injury. The mammalian spinal cord shows very limited regeneration and neurogenesis, resulting in permanent life-long functional impairment. Therefore, there is an urgent need to identify the cellular and molecular mechanisms that can drive efficient vertebrate neurogenesis following injury. A key pathway implicated in zebrafish neurogenesis is fibroblast growth factor signaling. Methods: In the present study we investigated the roles of distinctfibroblastgrowthfactormembersandtheir receptors in facilitating different aspects of neural development and regeneration at different timepoints following spinal cord injury. After spinal cord injury in adults and during larval development, loss and/or gain of Fgf signaling was combined with immunohistochemistry, in situ hybridization and transgenes marking motor neuron populations in in vivo zebrafish and in vitro mammalian PC12 cell culture models. Results: Fgf3 drives neurogenesis of Islet1 expressing motor neuron subtypes and mediate axonogenesis in cMet expressing motor neuron subtypes. We also demonstrate that the role of Fgf members are not necessarily simple recapitulating development. During development Fgf2, Fgf3 and Fgf8 mediate neurogenesis of Islet1 expressing neurons and neuronal sprouting of both, Islet1 and cMet expressing motor neurons.
    [Show full text]
  • Instability Restricts Signaling of Multiple Fibroblast Growth Factors
    Cell. Mol. Life Sci. DOI 10.1007/s00018-015-1856-8 Cellular and Molecular Life Sciences RESEARCH ARTICLE Instability restricts signaling of multiple fibroblast growth factors Marcela Buchtova • Radka Chaloupkova • Malgorzata Zakrzewska • Iva Vesela • Petra Cela • Jana Barathova • Iva Gudernova • Renata Zajickova • Lukas Trantirek • Jorge Martin • Michal Kostas • Jacek Otlewski • Jiri Damborsky • Alois Kozubik • Antoni Wiedlocha • Pavel Krejci Received: 18 June 2014 / Revised: 7 February 2015 / Accepted: 9 February 2015 Ó Springer Basel 2015 Abstract Fibroblast growth factors (FGFs) deliver ex- failure to activate FGF receptor signal transduction over tracellular signals that govern many developmental and long periods of time, and influence specific cell behavior regenerative processes, but the mechanisms regulating FGF in vitro and in vivo. Stabilization via exogenous heparin signaling remain incompletely understood. Here, we ex- binding, introduction of stabilizing mutations or lowering plored the relationship between intrinsic stability of FGF the cell cultivation temperature rescues signaling of un- proteins and their biological activity for all 18 members of stable FGFs. Thus, the intrinsic ligand instability is an the FGF family. We report that FGF1, FGF3, FGF4, FGF6, important elementary level of regulation in the FGF sig- FGF8, FGF9, FGF10, FGF16, FGF17, FGF18, FGF20, and naling system. FGF22 exist as unstable proteins, which are rapidly de- graded in cell cultivation media. Biological activity of Keywords Fibroblast growth factor Á FGF Á Unstable Á FGF1, FGF3, FGF4, FGF6, FGF8, FGF10, FGF16, FGF17, Proteoglycan Á Regulation and FGF20 is limited by their instability, manifesting as Electronic supplementary material The online version of this article (doi:10.1007/s00018-015-1856-8) contains supplementary material, which is available to authorized users.
    [Show full text]
  • Expression of Fibroblast Growth Factor 9 in Normal Human Lung and Idiopathic Pulmonary Fibrosis
    JHCXXX10.1369/0022155413497366Coffey et al.FGF9 in IPF 497366research-article2013 Article Journal of Histochemistry & Cytochemistry 61(9) 671 –679 © The Author(s) 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1369/0022155413497366 jhc.sagepub.com Expression of Fibroblast Growth Factor 9 in Normal Human Lung and Idiopathic Pulmonary Fibrosis Emily Coffey, Donna R. Newman, and Philip L. Sannes Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina Summary The fibroblast growth factor (FGF) family of signaling ligands contributes significantly to lung development and maintenance in the adult. FGF9 is involved in control of epithelial branching and mesenchymal proliferation and expansion in developing lungs. However, its activity and expression in the normal adult lung and by epithelial and interstitial cells in fibroproliferative diseases like idiopathic pulmonary fibrosis (IPF) are unknown. Tissue samples from normal organ donor human lungs and those of a cohort of patients with mild to severe IPF were sectioned and stained for the immunolocalization of FGF9. In normal lungs, FGF9 was confined to smooth muscle surrounding airways, alveolar ducts and sacs, and blood vessels. In addition to these same sites, lungs of IPF patients expressed FGF9 in a population of myofibroblasts within fibroblastic foci, hypertrophic and hyperplastic epithelium of airways and alveoli, and smooth muscle cells surrounding vessels embedded in thickened interstitium. The results demonstrate that FGF9 protein increased in regions of active cellular hyperplasia, metaplasia, and fibrotic expansion of IPF lungs, and in isolated human lung fibroblasts treated with TGF- β1 and/or overexpressing Wnt7B.
    [Show full text]
  • FGF Signaling Regulates Mesenchymal Differentiation and Skeletal Patterning Along the Limb Bud Proximodistal Axis Kai Yu and David M
    RESEARCH ARTICLE 483 Development 135, 483-491 (2008) doi:10.1242/dev.013268 FGF signaling regulates mesenchymal differentiation and skeletal patterning along the limb bud proximodistal axis Kai Yu and David M. Ornitz* Fibroblast growth factors (FGFs) are signals from the apical ectodermal ridge (AER) that are essential for limb pattern formation along the proximodistal (PD) axis. However, how patterning along the PD axis is regulated by AER-FGF signals remains controversial. To further explore the molecular mechanism of FGF functions during limb development, we conditionally inactivated fgf receptor 2 (Fgfr2) in the mouse AER to terminate all AER functions; for comparison, we inactivated both Fgfr1 and Fgfr2 in limb mesenchyme to block mesenchymal AER-FGF signaling. We also re-examined published data in which Fgf4 and Fgf8 were inactivated in the AER. We conclude that limb skeletal phenotypes resulting from loss of AER-FGF signals cannot simply be a consequence of excessive mesenchymal cell death, as suggested by previous studies, but also must be a consequence of reduced mesenchymal proliferation and a failure of mesenchymal differentiation, which occur following loss of both Fgf4 and Fgf8. We further conclude that chondrogenic primordia formation, marked by initial Sox9 expression in limb mesenchyme, is an essential component of the PD patterning process and that a key role for AER-FGF signaling is to facilitate SOX9 function and to ensure progressive establishment of chondrogenic primordia along the PD axis. KEY WORDS: FGF, FGF receptor, Apical ectodermal ridge (AER), Limb bud development, Chondrogenesis INTRODUCTION Previous studies indicate that AER-FGF signals are important The apical ectodermal ridge (AER) is a specialized ectodermal for maintaining mesenchymal cell survival during limb structure formed at the distal tip of the vertebrate limb bud that is development (Boulet et al., 2004; Sun et al., 2002).
    [Show full text]
  • FGF Signaling Network in the Gastrointestinal Tract (Review)
    163-168 1/6/06 16:12 Page 163 INTERNATIONAL JOURNAL OF ONCOLOGY 29: 163-168, 2006 163 FGF signaling network in the gastrointestinal tract (Review) MASUKO KATOH1 and MASARU KATOH2 1M&M Medical BioInformatics, Hongo 113-0033; 2Genetics and Cell Biology Section, National Cancer Center Research Institute, Tokyo 104-0045, Japan Received March 29, 2006; Accepted May 2, 2006 Abstract. Fibroblast growth factor (FGF) signals are trans- Contents duced through FGF receptors (FGFRs) and FRS2/FRS3- SHP2 (PTPN11)-GRB2 docking protein complex to SOS- 1. Introduction RAS-RAF-MAPKK-MAPK signaling cascade and GAB1/ 2. FGF family GAB2-PI3K-PDK-AKT/aPKC signaling cascade. The RAS~ 3. Regulation of FGF signaling by WNT MAPK signaling cascade is implicated in cell growth and 4. FGF signaling network in the stomach differentiation, the PI3K~AKT signaling cascade in cell 5. FGF signaling network in the colon survival and cell fate determination, and the PI3K~aPKC 6. Clinical application of FGF signaling cascade in cell polarity control. FGF18, FGF20 and 7. Clinical application of FGF signaling inhibitors SPRY4 are potent targets of the canonical WNT signaling 8. Perspectives pathway in the gastrointestinal tract. SPRY4 is the FGF signaling inhibitor functioning as negative feedback apparatus for the WNT/FGF-dependent epithelial proliferation. 1. Introduction Recombinant FGF7 and FGF20 proteins are applicable for treatment of chemotherapy/radiation-induced mucosal injury, Fibroblast growth factor (FGF) family proteins play key roles while recombinant FGF2 protein and FGF4 expression vector in growth and survival of stem cells during embryogenesis, are applicable for therapeutic angiogenesis. Helicobacter tissues regeneration, and carcinogenesis (1-4).
    [Show full text]
  • Age-Driven Developmental Drift in the Pathogenesis of Idiopathic Pulmonary Fibrosis
    BACK TO BASICS INTERSTITIAL LUNG DISEASES | Age-driven developmental drift in the pathogenesis of idiopathic pulmonary fibrosis Moisés Selman1, Carlos López-Otín2 and Annie Pardo3 Affiliations: 1Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico city, Mexico. 2Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain. 3Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico city, Mexico. Correspondence: Moisés Selman, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, CP 14080, México DF, México. E-mail: [email protected] ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal disease of unknown aetiology. A growing body of evidence supports that IPF represents an epithelial-driven process characterised by aberrant epithelial cell behaviour, fibroblast/myofibroblast activation and excessive accumulation of extracellular matrix with the subsequent destruction of the lung architecture. The mechanisms involved in the abnormal hyper-activation of the epithelium are unclear, but we propose that recapitulation of pathways and processes critical to embryological development associated with a tissue specific age-related stochastic epigenetic drift may be implicated. These pathways may also contribute to the distinctive behaviour of IPF fibroblasts. Genomic and epigenomic studies have revealed that wingless/ Int, sonic hedgehog and other developmental signalling pathways are reactivated and deregulated in IPF. Moreover, some of these pathways cross-talk with transforming growth factor-β activating a profibrotic feedback loop. The expression pattern of microRNAs is also dysregulated in IPF and exhibits a similar expression profile to embryonic lungs. In addition, senescence, a process usually associated with ageing, which occurs early in alveolar epithelial cells of IPF lungs, likely represents a conserved programmed developmental mechanism.
    [Show full text]
  • Alternative Splicing Generates an Isoform of the Human Sef Gene with Altered Subcellular Localization and Specificity
    Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity Ella Preger*, Inbal Ziv*, Ariel Shabtay*, Ifat Sher*, Michael Tsang†, Igor B. Dawid†, Yael Altuvia‡, and Dina Ron*§ *Department of Biology, Technion–Israel Institute of Technology, Haifa 32000, Israel; †Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and ‡Department of Molecular Genetics and Biotechnology, Hebrew University–Hadassah Medical School, Jerusalem 91120, Israel Contributed by Igor B. Dawid, December 1, 2003 Receptor tyrosine kinases (RTKs) control a multitude of biological FGFs comprise a family of 22 structurally related polypeptide processes and are therefore subjected to multiple levels of regu- mitogens that control cell proliferation, differentiation, survival, lation. Negative feedback is one of the mechanisms that provide an and migration and play a key role in embryonic patterning effective means to control RTK-mediated signaling. Sef has re- (14–16). They signal via binding and activation of a family of cently been identified as a specific antagonist of fibroblast growth cell-surface tyrosine kinase receptors designated FGF receptors factor (FGF) signaling in zebrafish and subsequently in mouse and 1–4 (FGFR1–FGFR4) (17–20). Activated receptors trigger sev- human. Sef encodes a putative type I transmembrane protein that eral signal transduction cascades including the Ras͞MAPK and antagonizes the Ras͞mitogen-activated protein kinase pathway in the PI3-kinase pathway (15, 21). Depending on the cell type, all three species. Mouse Sef was also shown to inhibit the phos- FGF can also activate other MAPK pathways, such that leading phatidylinositol 3-kinase pathway.
    [Show full text]
  • A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease in Type 2 Diabetes
    University of Louisville ThinkIR: The University of Louisville's Institutional Repository Electronic Theses and Dissertations 8-2018 A novel fibroblast growth factor 1 variant reverses nonalcoholic fatty liver disease in type 2 diabetes. Qian Lin University of Louisville Follow this and additional works at: https://ir.library.louisville.edu/etd Part of the Endocrine System Diseases Commons, and the Pharmacology Commons Recommended Citation Lin, Qian, "A novel fibroblast growth factor 1 variant reverses nonalcoholic fatty liver disease in type 2 diabetes." (2018). Electronic Theses and Dissertations. Paper 3016. https://doi.org/10.18297/etd/3016 This Doctoral Dissertation is brought to you for free and open access by ThinkIR: The University of Louisville's Institutional Repository. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of ThinkIR: The University of Louisville's Institutional Repository. This title appears here courtesy of the author, who has retained all other copyrights. For more information, please contact [email protected]. A NOVEL FIBROBLAST GROWTH FACTOR 1 VARIANT REVERSES NONALCOHOLIC FATTY LIVER DISEASE IN TYPE 2 DIABETES BY Qian Lin M.S. at Wenzhou Medical University, 2016 A Dissertation Submitted to the Faculty of the School of Medicine of the University of Louisville for the Degree of Doctor of Philosophy in Pharmacology and Toxicology Department of Pharmacology and Toxicology University of Louisville Louisville, Kentucky August 2018 A NOVEL FIBROBLAST GROWTH FACTOR 1 VARIANT REVERSES NONALCOHOLIC FATTY LIVER DISEASE IN TYPE 2 DIABETES BY Qian Lin Dissertation Approved on August 2, 2018 Dissertation Committee: Dr. Yi Tan Dr. Paul Epstein Dr.
    [Show full text]
  • The Roles of Fgfs in the Early Development of Vertebrate Limbs
    Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW The roles of FGFs in the early development of vertebrate limbs Gail R. Martin1 Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, California 94143–0452 USA ‘‘Fibroblast growth factor’’ (FGF) was first identified 25 tion of two closely related proteins—acidic FGF and ba- years ago as a mitogenic activity in pituitary extracts sic FGF (now designated FGF1 and FGF2, respectively). (Armelin 1973; Gospodarowicz 1974). This modest ob- With the advent of gene isolation techniques it became servation subsequently led to the identification of a large apparent that the Fgf1 and Fgf2 genes are members of a family of proteins that affect cell proliferation, differen- large family, now known to be comprised of at least 17 tiation, survival, and motility (for review, see Basilico genes, Fgf1–Fgf17, in mammals (see Coulier et al. 1997; and Moscatelli 1992; Baird 1994). Recently, evidence has McWhirter et al. 1997; Hoshikawa et al. 1998; Miyake been accumulating that specific members of the FGF 1998). At least five of these genes are expressed in the family function as key intercellular signaling molecules developing limb (see Table 1). The proteins encoded by in embryogenesis (for review, see Goldfarb 1996). Indeed, the 17 different FGF genes range from 155 to 268 amino it may be no exaggeration to say that, in conjunction acid residues in length, and each contains a conserved with the members of a small number of other signaling ‘‘core’’ sequence of ∼120 amino acids that confers a com- molecule families [including WNT (Parr and McMahon mon tertiary structure and the ability to bind heparin or 1994), Hedgehog (HH) (Hammerschmidt et al.
    [Show full text]
  • Upregulated Expression of FGF13/FHF2 Mediates Resistance To
    OPEN Upregulated expression of FGF13/FHF2 SUBJECT AREAS: mediates resistance to platinum drugs in CANCER THERAPEUTIC RESISTANCE cervical cancer cells CANCER PREVENTION Tomoko Okada1, Kazuhiro Murata1,2, Ryoma Hirose1,3, Chie Matsuda1, Tsunehiko Komatsu2, STRESS SIGNALLING Masahiko Ikekita3, Miyako Nakawatari4, Fumiaki Nakayama4, Masaru Wakatsuki5, Tatsuya Ohno5,6, CHEMOTHERAPY Shingo Kato5,7, Takashi Imai4 & Toru Imamura1,3 Received 1Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and 27 June 2013 2 Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan, Division of Hematology, 3rd Department of Internal Medicine, Teikyo 3 Accepted University Chiba Medical Center, Ichihara, Chiba 299-0111, Japan, Department of Applied Biological Science, Faculty of Science 4 18 September 2013 and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan, Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, Chiba, Chiba 263-8555, Japan, 5Research Center Hospital for Charged Particle Published Therapy, National Institute of Radiological Sciences, Chiba, Chiba 263-8555, Japan, 6Gunma University Graduate School of 11 October 2013 Medicine, Maebashi, Gunma 371-8511, Japan, 7Saitama Medical University International Medical Center, Hidaka, Saitama 350- 1298, Japan. Correspondence and Cancer cells often develop drug resistance. In cisplatin-resistant HeLa cisR cells, fibroblast growth factor 13 requests for materials (FGF13/FHF2) gene and protein expression was strongly upregulated, and intracellular platinum should be addressed to concentrations were kept low. When the FGF13 expression was suppressed, both the cells’ resistance to T.Imamura (imamura- platinum drugs and their ability to keep intracellular platinum low were abolished. Overexpression of [email protected]) FGF13 in parent cells led to greater resistance to cisplatin and reductions in the intracellular platinum concentration.
    [Show full text]