DOCSLIB.ORG

Fgf10 Dosage Is Critical for the Amplification of Epithelial Cell Progenitors and for the Formation of Multiple Mesenchymal Lineages During Lung Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Fgf10 Dosage Is Critical for the Amplification of Epithelial Cell Progenitors and for the Formation of Multiple Mesenchymal Lineages During Lung Development Developmental Biology 307 (2007) 237–247 www.elsevier.com/locate/ydbio Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development Suresh K. Ramasamy a,1, Arnaud A. Mailleux b,1, Varsha V. Gupte a, Francisca Mata a, Frédéric G. Sala a, Jacqueline M. Veltmaat c, Pierre M. Del Moral a, Stijn De Langhe a, Sara Parsa a, Lisa K. Kelly d, Robert Kelly e, Wei Shia a, Eli Keshet f, Parviz Minoo g, ⁎ David Warburton a, Savério Bellusci a, a Developmental Biology Program, Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA b Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA c Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore d Division of Pediatrics, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA e Developmental Biology Institute of Marseille Luminy-UMR6216-CNRS-Université de la Méditerranée, France f Department of Molecular Biology, The Hebrew University–Hadassah Medical School, Jerusalem, Israel g Department of Pediatrics, Women's and Children's Hospital, USC Keck School of Medicine, Los Angeles, CA 90033, USA Received for publication 23 October 2006; revised 24 April 2007; accepted 26 April 2007 Available online 3 May 2007 Abstract The key role played by Fgf10 during early lung development is clearly illustrated in Fgf10 knockout mice, which exhibit lung agenesis. However, Fgf10 is continuously expressed throughout lung development suggesting extended as well as additional roles for FGF10 at later stages of lung organogenesis. We previously reported that the enhancer trap Mlcv1v-nLacZ-24 transgenic mouse strain functions as a reporter for Fgf10 expression and displays decreased endogenous Fgf10 expression. In this paper, we have generated an allelic series to determine the impact of Fgf10 dosage on lung development. We report that 80% of the newborn Fgf10 hypomorphic mice die within 24 h of birth due to respiratory failure. These mutant mouse lungs display severe hypoplasia, dilation of the distal airways and large hemorrhagic areas. Epithelial differentiation and proliferation studies indicate a specific decrease in TTF1 and SP-B expressing cells correlating with reduced epithelial cell proliferation and associated with a decrease in activation of the canonical Wnt signaling in the epithelium. Analysis of vascular development shows a reduction in PECAM expression at E14.5, which is associated with a simplification of the vascular tree at E18.5. We also show a decrease in α-SMA expression in the respiratory airway suggesting defective smooth muscle cell formation. At the molecular level, these defects are associated with decrease in Vegfa and Pdgfa expression likely resulting from the decrease of the epithelial/ mesenchymal ratio in the Fgf10 hypomorphic lungs. Thus, our results indicate that FGF10 plays a pivotal role in maintaining epithelial progenitor cell proliferation as well as coordinating alveolar smooth muscle cell formation and vascular development. © 2007 Elsevier Inc. All rights reserved. Keywords: Fgf10 hypomorph; Mesenchymal differentiation; Smooth muscle cells; Lung emphysema; Vascularization Introduction sites where prospective epithelial buds will appear. Moreover, its dynamic pattern of expression and its ability to induce epithelial Fibroblast growth factor 10 (FGF10) is responsible for directed expansion and budding in organ cultures have led to the outgrowth of the lung endoderm (Bellusci et al., 1997). In the hypothesis that FGF10 governs the directional outgrowth of developing lung, Fgf10 is expressed in the distal mesenchyme at lung buds during branching morphogenesis (Bellusci et al., 1997). Furthermore, FGF10 was shown to induce chemotaxis of the ⁎ Corresponding author. distal lung epithelium (Park et al., 1998; Weaver et al., 2000). E-mail address: [email protected] (S. Bellusci). Consistent with these observations, Fgf10 null mutants show 1 Contributed equally to this work. multiple organ defects including lung agenesis (Min et al., 1998; 0012-1606/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ydbio.2007.04.033 238 S.K. Ramasamy et al. / Developmental Biology 307 (2007) 237–247 Sekine et al., 1999), therefore hampering the study of subsequent desired stages and fixed in 4% PFA. Following fixation, the embryos were FGF10 role during lung development. FGF10 is the main ligand washed in 1× PBS and stained with X-gal solution. Stained lungs were sectioned (25μm) using a vibratome. for fibroblast growth factor receptor 2b (FGFR2b) during embryonic development as demonstrated by the remarkable Mutant embryos similarity of phenotypes exhibited by embryos where these genes have been inactivated (Min et al., 1998; Sekine et al., 1999; Burns The Mlc1v-nLacZ-24 line (called for simplification Mlc1v-LacZ or Mlc1v in et al., 2004; De Moerlooze et al., 2000; Mailleux et al., 2002; this paper) has been previously described (Kelly et al., 2001). The transgene containing an nLacZ reporter gene (containing a nuclear localization signal) is Burns et al., 2004; Del Moral et al., 2006a,b). Moreover, integrated upstream of the Fgf10 gene. Fgf10+/−;Mlc1v-LacZ+/− embryos were inhibition of FGFR2b signaling from embryonic day 14.5 generated by crossing Fgf10+/− and Mlc1v-LacZ+/− mice (Kelly et al., 2001; (E14.5) onwards using a transgenic mouse line expressing a Sekine et al., 1999) on a C57BL/6 background. Fgf10+/− littermates were used as − soluble FGFR2b (FGFR2b-HFc) under the control of an control embryos at different developmental stages. The Fgf10 and Mlc1v-LacZ+ inducible lung-specific, Surfactant protein C promoter (SpC- alleles were genotyped as described previously (Kelly et al., 2001; Mailleux et al., 2002). The number of Fgf10+/−;Mlc1v-LacZ+/− embryos used in this study (47 in rtTA), resulted in decreased epithelial morphogenesis before total) at the different stages was as follows: E12.5 (n=7), E13.5 (n=3), E14.5 birth and caused severe emphysema at maturity (Hokuto et al., (n=6), E16.5 (n=2), E17.5 (n=10); E18.5 (n=7); PN (n=12). 2003). Interestingly, Fgf10 expression level keeps increasing during lung development between E11.5 and E18.5 (Bellusci et Real-time RT–PCR al., 1997), suggesting that Fgf10 most likely plays an extended +/− +/− +/− and vital role during late lung organogenesis. Total RNA was extracted from individual Fgf10 and Fgf10 ;Mlc1v E14.5 embryonic lungs (n=3 for each genotype) using the RNeasy kit (Gibco We have previously shown that a transgenic mouse line with BRL) according to the manufacturer's instructions. DNA contaminations were the β-galactosidase gene under the control of Fgf10 regulatory removed in the total RNA using Turbo DNAse (Ambion). Total RNA was sequences can be used to monitor Fgf10 expression in the heart, reverse-transcribed using the Superscript-III first strand super mix (Invitrogen) lung and somites (Kelly et al., 2001; Mailleux et al., 2005; following the manufacturer's recommendations. 5 μg of the total RNA was used Veltmaat et al., 2006). Originally, Kelly et al. (2001) sought to to prepare cDNA from the isolated total RNA using oligodT primers. 25 pg cDNA was used for each of the real-time PCR reactions using the primers and express LacZ under the control of the myocardial ventricular- probes designed by the online Roche software: Probe finder version 2.20, https:// slow skeletal muscle Myosin Alkali-light chain (Mlc1v)promoter. www.roche-applied%1Escience.com/sis/rtpcr/upl/adc.jsp. All real-time PCR reac- In one of four founders, the expression pattern in the developing tions were performed with Roche: FastStart TaqMan® Probe Master kits, according heart suggested that LacZ was under the control of Fgf10 to the manufacturer's instructions in Roche Light Cycler 1.5 Real-Time PCR regulatory sequences. In addition, analysis of the integration site machine. 18S ribosomal RNA was used as an internal control for all analysis. showed that the Mlc1v-LacZ cassette had integrated 120 kb Analysis of SP-B and TTF-1 expression upstream of the Fgf10 gene. Based on the expression pattern as well as on the site of insertion, the authors proposed that LacZ Newborn pup lungs (3 Fgf10+/−;Mlc1v-LacZ+/− and 3 control) were fixed expression was under the control of Fgf10 regulatory sequences. overnight in paraformaldehyde, rinsed in PBS twice for 5 min, transferred to 70% We reported that the insertion of the Mlc1v-LacZ cassette ethanol overnight and stored in 100% ethanol. The samples were then embedded in paraffin and sections (5 μm) were cut. The number of cells expressing SP-B disrupted the endogenous expression of Fgf10 (Mailleux et al., and TTF1 was quantified using immunohistochemistry protocol with Envision+ +/− 2005). The Mlc1v-LacZ mice were crossed with Fgf10 mice to HRP system (Dakocytomation). Alternatively, expression of SP-B was also generate an allelic series to determine the effect of decreasing determined using in situ hybridization on sections using a specific mouse SP-B Fgf10 expression on parabronchial smooth muscle cell formation. probe (gift from Dr. Jeffrey Whitsett). Positive cells were scored in random We also demonstrated that Fgf10 identifies a new population of portions of a section in eight photomicrographs (50× magnification). A total number of 3000 cells were counted per sample. The results are presented as a ratio parabronchial smooth muscle cell progenitors located in the sub- of total number of positive cells/total number of cells. Lungs from three mutant mesothelial mesenchyme (Mailleux et al., 2005). and three control mice were taken at birth. In this paper, we report our analysis of Fgf10 hypomorphic (Fgf10+/−;Mlc1v-LacZ+/−) lungs at various developmental Antibodies stages. Newborn Fgf10 hypomorphic mice exhibit respiratory μ failure and consequently die within 48 h. Analysis shows The following antibodies were used for immunohistochemistry on 5 m thick paraffin sections: mouse monoclonal antibody against α-SMA (Sigma) at a severe lung hypoplasia, dilation of the distal airways and large dilution of 1/5000, mouse monoclonal antibody against Phospho-p44/42 MAPK hemorrhagic areas.
Load more

Recommended publications
  • Structural and Functional Properties of Platelet-Derived Growth Factor and Stem Cell Factor Receptors
    Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press Structural and Functional Properties of Platelet-Derived Growth Factor and Stem Cell Factor Receptors Carl-Henrik Heldin and Johan Lennartsson Ludwig Institute for Cancer Research, Uppsala University, SE-751 24 Uppsala, Sweden Correspondence: [email protected] The receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF) are members of the type III class of PTK receptors, which are characterized by five Ig-like domains extracellularly and a split kinase domain intracellularly. The receptors are activated by ligand-induced dimerization, leading to autophosphorylation on specific tyrosine resi- dues. Thereby the kinase activities of the receptors are activated and docking sites for down- stream SH2 domain signal transduction molecules are created; activation of these pathways promotes cell growth, survival, and migration. These receptors mediate important signals during the embryonal development, and control tissue homeostasis in the adult. Their over- activity is seen in malignancies and other diseases involving excessive cell proliferation, such as atherosclerosis and fibrotic diseases. In cancer, mutations of PDGF and SCF receptors— including gene fusions, point mutations, and amplifications—drive subpopulations of cer- tain malignancies, such as gastrointestinal stromal tumors, chronic myelomonocytic leuke- mia, hypereosinophilic syndrome, glioblastoma, acute myeloid leukemia, mastocytosis, and melanoma. he type III tyrosine kinase receptor family with kinases, and a less well-conserved carboxy- Tconsists of platelet-derived growth factor terminal tail. The ligands for these receptors are (PDGF) receptor a and b, stem cell factor all dimeric molecules, and on binding they in- (SCF) receptor (Kit), colony-stimulating fac- duce receptor dimerization.
    [Show full text]
  • Type of the Paper (Article
    Table S1. Gene expression of pro-angiogenic factors in tumor lymph nodes of Ibtk+/+Eµ-myc and Ibtk+/-Eµ-myc mice. Fold p- Symbol Gene change value 0,007 Akt1 Thymoma viral proto-oncogene 1 1,8967 061 0,929 Ang Angiogenin, ribonuclease, RNase A family, 5 1,1159 481 0,000 Angpt1 Angiopoietin 1 4,3916 117 0,461 Angpt2 Angiopoietin 2 0,7478 625 0,258 Anpep Alanyl (membrane) aminopeptidase 1,1015 737 0,000 Bai1 Brain-specific angiogenesis inhibitor 1 4,0927 202 0,001 Ccl11 Chemokine (C-C motif) ligand 11 3,1381 149 0,000 Ccl2 Chemokine (C-C motif) ligand 2 2,8407 298 0,000 Cdh5 Cadherin 5 2,5849 744 0,000 Col18a1 Collagen, type XVIII, alpha 1 3,8568 388 0,003 Col4a3 Collagen, type IV, alpha 3 2,9031 327 0,000 Csf3 Colony stimulating factor 3 (granulocyte) 4,3332 258 0,693 Ctgf Connective tissue growth factor 1,0195 88 0,000 Cxcl1 Chemokine (C-X-C motif) ligand 1 2,67 21 0,067 Cxcl2 Chemokine (C-X-C motif) ligand 2 0,7507 631 0,000 Cxcl5 Chemokine (C-X-C motif) ligand 5 3,921 328 0,000 Edn1 Endothelin 1 3,9931 042 0,001 Efna1 Ephrin A1 1,6449 601 0,002 Efnb2 Ephrin B2 2,8858 042 0,000 Egf Epidermal growth factor 1,726 51 0,000 Eng Endoglin 0,2309 467 0,000 Epas1 Endothelial PAS domain protein 1 2,8421 764 0,000 Ephb4 Eph receptor B4 3,6334 035 V-erb-b2 erythroblastic leukemia viral oncogene homolog 2, 0,000 Erbb2 3,9377 neuro/glioblastoma derived oncogene homolog (avian) 024 0,000 F2 Coagulation factor II 3,8295 239 1 0,000 F3 Coagulation factor III 4,4195 293 0,002 Fgf1 Fibroblast growth factor 1 2,8198 748 0,000 Fgf2 Fibroblast growth factor
    [Show full text]
  • Single-Cell Transcriptome Sequencing of 18,787 Human Induced Pluripotent Stem Cells Identifies Differentially Primed Subpopulations
    Single-cell transcriptome sequencing of 18,787 human induced pluripotent stem cells identifies differentially primed subpopulations Quan H. Nguyen1*, Samuel W. Lukowski1*, Han Sheng Chiu1, Anne Senabouth1, Timothy J. C. Bruxner1, Angelika N. Christ1, Nathan J. Palpant1*, Joseph E. Powell1,2* 1 Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia 2 Queensland Brain Institute, University of Queensland, Brisbane, Australia * These authors contributed equally Supplementary Figures and Tables Table S1. Summary statistics for sequencing and mapping data of five samples Mean Median Total Median Percent Remaining Number Total number reads per genes genes UMIs per mapped cells post of cells of reads cell per cell detected cell reads filtering Sample 1 2,779 71,256 3,662 20,356 17,769 198,022,303 62.6 2,426 Sample 2 545 318,909 4,547 18,557 27,341 173,805,798 63.4 424 Sample 3 3,103 56,459 2,944 19,261 11,214 175,193,813 71.8 2,906 Sample 4 9,192 38,637 2,016 21,491 5,963 355,158,219 68.9 8,294 Sample 5 4,863 26,471 2,804 20,235 10,150 128,728,889 67.2 4,737 1 Table S2. Summary of the cell and gene filtering process Procedure Count Cells removed by library size (outside 3 x MAD range)a 0 Cells removed by number detected genes (outside 3 x MAD range) 77 Cells removed by reads mapped to mitochondrial genes (outside 3 x MAD range) 1,559 Cells removed by reads mapped to ribosomal genes (outside 3 x MAD range) 102 Cells removed by reads mapped to mitochondrial genes (> 20 % total reads)b 0 Cells removed by reads mapped to ribosomal genes (> 50 % total reads) 0 Genes removed by number of expressed cells (< 1 % total cells)c 16,674 Remaining cells post filtering 18,787 Remaining genes post filtering 16,064 aMAD stands for median absolute deviation.
    [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]
  • Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile
    Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile Julien Patenaude and Claude Perreault This information is current as J Immunol 2016; 196:4760-4770; Prepublished online 29 of October 1, 2021. April 2016; doi: 10.4049/jimmunol.1502499 http://www.jimmunol.org/content/196/11/4760 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2016/04/29/jimmunol.150249 Material 9.DCSupplemental References This article cites 65 articles, 18 of which you can access for free at: http://www.jimmunol.org/content/196/11/4760.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 1, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile Julien Patenaude and Claude Perreault In order to understand the role of mesenchymal cells (MCs) in the adult thymus, we performed whole transcriptome analyses of primary thymic, bone, and skin MCs.
    [Show full text]
  • PDGFRA in Vascular Adventitial Mscs Promotes Neointima Formation in Arteriovenous Fistula in Chronic Kidney Disease
    RESEARCH ARTICLE PDGFRA in vascular adventitial MSCs promotes neointima formation in arteriovenous fistula in chronic kidney disease Ke Song,1,2 Ying Qing,2 Qunying Guo,2 Eric K. Peden,3 Changyi Chen,4 William E. Mitch,2 Luan Truong,5 and Jizhong Cheng2 1Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. 3Department of Vascular Surgery, DeBakey Heart and Vascular Institute, Houston Methodist Hospital, Houston, Texas, USA. 4Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA. 5Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA. Chronic kidney disease (CKD) induces the failure of arteriovenous fistulas (AVFs) and promotes the differentiation of vascular adventitial GLI1-positive mesenchymal stem cells (GMCs). However, the roles of GMCs in forming neointima in AVFs remain unknown. GMCs isolated from CKD mice showed increased potential capacity of differentiation into myofibroblast-like cells. Increased activation of expression of PDGFRA and hedgehog (HH) signaling were detected in adventitial cells of AVFs from patients with end-stage kidney disease and CKD mice. PDGFRA was translocated and accumulated in early endosome when sonic hedgehog was overexpressed. In endosome, PDGFRA-mediated activation of TGFB1/SMAD signaling promoted the differentiation of GMCs into myofibroblasts, extracellular matrix deposition, and vascular fibrosis. These responses resulted in neointima formation and AVF failure. KO of Pdgfra or inhibition of HH signaling in GMCs suppressed the differentiation of GMCs into myofibroblasts. In vivo, specific KO of Pdgfra inhibited GMC activation and vascular fibrosis, resulting in suppression of neointima formation and improvement of AVF patency despite CKD.
    [Show full text]
  • Ep 3217179 A1
    (19) TZZ¥ ___T (11) EP 3 217 179 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 13.09.2017 Bulletin 2017/37 G01N 33/68 (2006.01) (21) Application number: 17167637.2 (22) Date of filing: 02.10.2013 (84) Designated Contracting States: • LIU, Xinjun AL AT BE BG CH CY CZ DE DK EE ES FI FR GB San Diego, CA 92130 (US) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • HAUENSTEIN, Scott PL PT RO RS SE SI SK SM TR San Diego, CA 92130 (US) • KIRKLAND, Richard (30) Priority: 05.10.2012 US 201261710491 P San Diego, CA 92111 (US) 17.05.2013 US 201361824959 P (74) Representative: Krishnan, Sri (62) Document number(s) of the earlier application(s) in Nestec S.A. accordance with Art. 76 EPC: Centre de Recherche Nestlé 13779638.9 / 2 904 405 Vers-chez-les-Blanc Case Postale 44 (71) Applicant: Nestec S.A. 1000 Lausanne 26 (CH) 1800 Vevey (CH) Remarks: (72) Inventors: This application was filed on 21-04-2017 as a • SINGH, Sharat divisional application to the application mentioned Rancho Santa Fe, CA 92127 (US) under INID code 62. (54) METHODS FOR PREDICTING AND MONITORING MUCOSAL HEALING (57) The present invention provides methods for pre- an individual with a disease such as IBD. Information on dicting the likelihood of mucosal healing in an individual mucosal healing status derived from the use of the with a disease such as inflammatory bowel disease present invention can also aid in optimizing therapy (IBD).
    [Show full text]
  • Comparison of the Interactions of Different Growth Factors And
    molecules Article Comparison of the Interactions of Different Growth Factors and Glycosaminoglycans Fuming Zhang 1,* , Lanhong Zheng 2,3, Shuihong Cheng 2,4, Yanfei Peng 2,5, Li Fu 2, Xing Zhang 2,6 and Robert J. Linhardt 1,2,7,* 1 Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA 2 Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; [email protected] (L.Z.); [email protected] (S.C.); [email protected] (Y.P.); [email protected] (L.F.); [email protected] (X.Z.) 3 School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China 4 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China 5 College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China 6 School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Wenyuan Road 1, Nanjing 210023, China 7 Departments of Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA * Correspondence: [email protected] (F.Z.); [email protected] (R.J.L.); Tel.: +1-518-276-3404 (R.J.L.) Received: 20 August 2019; Accepted: 11 September 2019; Published: 16 September 2019 Abstract: Most growth factors are naturally occurring proteins, which are signaling molecules implicated in cellular multiple functions such as proliferation, migration and differentiation under patho/physiological conditions by interacting with cell surface receptors and other ligands in the extracellular microenvironment.
    [Show full text]
  • WO 2014/054013 Al 10 April 2014 (10.04.2014) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2014/054013 Al 10 April 2014 (10.04.2014) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every G01N 33/68 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/IB2013/059077 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KN, KP, KR, 2 October 2013 (02. 10.2013) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (30) Priority Data: ZW. 61/710,491 5 October 2012 (05. 10.2012) 61/824,959 17 May 2013 (17.05.2013) (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: NESTEC S.A. [CH/CH]; Ave. Nestle 55, CH- GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 1800 Vevey (CH).
    [Show full text]
  • Control Mechanisms of Lung Alveolar Development and Their Disorders in Bronchopulmonary Dysplasia
    0031-3998/05/5705-0038R PEDIATRIC RESEARCH Vol. 57, No. 5, Pt 2, 2005 Copyright © 2005 International Pediatric Research Foundation, Inc. Printed in U.S.A. Control Mechanisms of Lung Alveolar Development and Their Disorders in Bronchopulmonary Dysplasia JACQUES BOURBON, OLIVIER BOUCHERAT, BERNADETTE CHAILLEY-HEU, AND CHRISTOPHE DELACOURT Inserm U651-Université Paris XII, Faculté de Médecine, F-94010 Créteil, France ABSTRACT Bronchopulmonary dysplasia (BPD) is a chronic lung disease premature baboon or lamb, neonatal exposure to hyperoxia in that occurs in very premature infants and is characterized by rodents, and maternal-fetal infection. These findings open ther- impaired alveologenesis. This ultimate phase of lung develop- apeutic perspectives to correct imbalanced signaling. Unraveling ment is mostly postnatal and allows growth of gas-exchange the intimate molecular mechanisms of alveolar building appears surface area to meet the needs of the organism. Alveologenesis is as a prerequisite to define new strategies for the prevention and a highly integrated process that implies cooperative interactions care of BPD. (Pediatr Res 57: 38R–46R, 2005) between interstitial, epithelial, and vascular compartments of the lung. Understanding of its underlying mechanisms has consider- Abbreviations ably progressed recently with identification of structural, signal- BPD, bronchopulmonary dysplasia ing, or remodeling molecules that are crucial in the process. ECM, extracellular matrix Thus, the pivotal role of elastin deposition in lung walls has been EMAP II, endothelial-monocyte activating polypeptide II demonstrated, and many key control-molecules have been iden- FGF, fibroblast growth factor tified, including various transcription factors, growth factors such GC, glucocorticoids as platelet-derived growth factor, fibroblast growth factors, and MMP, matrix metalloproteinase vascular endothelial growth factor, matrix-remodeling enzymes, PDGF, platelet-derived growth factor and retinoids.
    [Show full text]
  • Expression of Fgfs During Early Mouse Tongue Development
    Gene Expression Patterns 20 (2016) 81e87 Contents lists available at ScienceDirect Gene Expression Patterns journal homepage: http://www.elsevier.com/locate/gep Expression of FGFs during early mouse tongue development * Wen Du a, b, Jan Prochazka b, c, Michaela Prochazkova b, c, Ophir D. Klein b, d, a State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China b Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA 94143, USA c Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, v.v.i., Prague, Czech Republic d Department of Pediatrics and Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA article info abstract Article history: The fibroblast growth factors (FGFs) constitute one of the largest growth factor families, and several Received 29 September 2015 ligands and receptors in this family are known to play critical roles during tongue development. In order Received in revised form to provide a comprehensive foundation for research into the role of FGFs during the process of tongue 13 December 2015 formation, we measured the transcript levels by quantitative PCR and mapped the expression patterns by Accepted 29 December 2015 in situ hybridization of all 22 Fgfs during mouse tongue development between embryonic days (E) 11.5 Available online 31 December 2015 and E14.5. During this period, Fgf5, Fgf6, Fgf7, Fgf9, Fgf10, Fgf13, Fgf15, Fgf16 and Fgf18 could all be detected with various intensities in the mesenchyme, whereas Fgf1 and Fgf2 were expressed in both the Keywords: Tongue epithelium and the mesenchyme.
    [Show full text]
  • Targeting the Platelet-Derived Growth Factor Receptor a with a Neutralizing
    Molecular Cancer Therapeutics 369 Targeting the platelet-derived growth factor receptor A with a neutralizing human monoclonal antibody inhibits the growth of tumor xenografts: Implications as a potential therapeutic target Nick Loizos, Yan Xu, Jim Huber, Meilin Liu, polypeptide chains that bind to two receptors simulta- Dan Lu, Bridget Finnerty, Robin Rolser, neously and induce receptor dimerization, autophosphor- Asra Malikzay, Anita Persaud, Erik Corcoran, ylation, and intracellular signaling. PDGFRa can form Dhanvanthri S. Deevi, Paul Balderes, Rajiv Bassi, homodimers as well as heterodimers with the structurally Xenia Jimenez, Christopher J. Joynes, similar PDGFRh. Given that PDGFRh does not bind the Venkata R.M. Mangalampalli, Philipp Steiner, PDGF-A chain with high affinity, PDGF-AA activates only James R. Tonra, Yan Wu, Daniel S. Pereira, aa receptor dimers, PDGF-AB and PDGF-CC activates aa Zhenping Zhu, Dale L. Ludwig, Daniel J. Hicklin, and ah receptor dimers, and PDGF-BB activates all three Peter Bohlen, Larry Witte, and Paul Kussie combinations of receptor dimers. A critical role for PDGFRa during early development is ImClone Systems Incorporated, New York, New York evident by the fact that mice homozygous for a null mutation die during embryogenesis. The homozygotes exhibit cranial Abstract malformations and a deficiency in myotome formation (3). a Platelet-derived growth factor receptor A (PDGFRA)isa At later stages of development, PDGFR is expressed in type III receptor tyrosine kinase that is expressed on a many mesenchymal structures, whereas adjacent epithelial variety of tumor types. A neutralizing monoclonal antibody cells produce PDGFs (reviewed in ref. 4). In the adult, to human PDGFRA, which did not cross-react with the hh PDGFs function in wound healing by activating mitogenesis, form of the receptor, was generated.
    [Show full text]