7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Involvement of Igf1r in Bronchiolar Epithelial Regeneration: Role during Repair Kinetics after Selective Club Cell Ablation

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice, and revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury.

          Related collections

          Most cited references74

          • Record: found
          • Abstract: found
          • Article: not found

          Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r).

          Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene (Igf-1) exhibit a growth deficiency similar in severity to that previously observed in viable Igf-2 null mutants (60% of normal birthweight). Depending on genetic background, some of the Igf-1(-/-) dwarfs die shortly after birth, while others survive and reach adulthood. In contrast, null mutants for the Igf1r gene die invariably at birth of respiratory failure and exhibit a more severe growth deficiency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis. Igf-1(-/-)/Igf1r(-/-) double mutants did not differ in phenotype from Igf1r(-/-) single mutants, while in Igf-2(-)/Igf1r(-/-) and Igf-1(-/-)/Igf-2(-) double mutants, which are phenotypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Preparing for the first breath: genetic and cellular mechanisms in lung development.

            The mammalian respiratory system--the trachea and the lungs--arises from the anterior foregut through a sequence of morphogenetic events involving reciprocal endodermal-mesodermal interactions. The lung itself consists of two highly branched, tree-like systems--the airways and the vasculature--that develop in a coordinated way from the primary bud stage to the generation of millions of alveolar gas exchange units. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as branching morphogenesis, vascular development, and the differentiation of multipotent progenitor populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding respiratory disorders, congenital defects in human neonates, and how the disruption of morphogenetic programs early in lung development can lead to deficiencies that persist throughout life. (c) 2010 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Fate mapping Nkx2.1-lineage cells in the mouse telencephalon.

              The homeodomain transcription factor Nkx2.1 is expressed in the pallidal (subcortical) telencephalon, including the medial ganglionic eminence (MGE) and preoptic area. Studies have shown that Nkx2.1 is required for normal patterning of the MGE and for the specification of the parvalbumin (PV)- and somatostatin (SST)-expressing cortical interneurons. To define the contribution of Nkx2.1 lineages to neurons in the mature telencephalon, we have generated transgenic mice carrying the genomic integration of a modified bacterial artificial chromosome (BAC) in which the second exon of Nkx2.1 is replaced by the Cre recombinase. Analysis of these mice has found that they express the Cre recombinase and Cre reporters within Nkx2.1-expressing domains of the brain, thyroid, pituitary, and lung. Telencephalic expression of reporters begins at about embryonic day 10.5. Expression both of Cre and of recombination-based Cre reporters is weaker within the dorsalmost region of the MGE than in other Nkx2.1-expressing regions. In this paper, we present fate-mapping data on Nkx2.1-lineage neurons throughout the telencephalon, including the cerebral cortex, amygdala, olfactory bulb, striatum, globus pallidus, septum, and nucleus basalis. Copyright 2007 Wiley-Liss, Inc.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 November 2016
                2016
                : 11
                : 11
                : e0166388
                Affiliations
                [1 ]Centro de Investigación Biomédica de la Rioja (CIBIR), Fundación Rioja Salud, Logroño, Spain
                [2 ]Institute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
                Children's Hospital of Los Angeles, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: IPL SP-H RSP JGP.

                • Data curation: IPL SP-H RSP RT AH JGP.

                • Funding acquisition: IPL SP-H AH JGP.

                • Investigation: IPL SP-H RSP AH JGP.

                • Methodology: IPL SP-H RSP RT AH JGP.

                • Project administration: JGP.

                • Resources: IPL SP-H RSP RT AH JGP.

                • Supervision: JGP.

                • Validation: IPL SP-H AH JGP.

                • Visualization: IPL SP-H RSP AH JGP.

                • Writing – original draft: IPL SP-H JGP.

                • Writing – review & editing: IPL SP-H AH JGP.

                Article
                PONE-D-16-34290
                10.1371/journal.pone.0166388
                5115747
                27861515
                27b2a272-599b-4f87-855d-8058cda79cf5
                © 2016 López et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 August 2016
                : 27 October 2016
                Page count
                Figures: 8, Tables: 0, Pages: 32
                Funding
                Funded by: Fundación Rioja Salud (Gobierno de La Rioja, Spain)
                Award Recipient : José García Pichel
                Funded by: Sistema Riojano de Innovación (Gobierno de La Rioja, Spain)
                Award Recipient :
                S.P.-H. thanks the Sistema Riojano de Innovación (Gobierno de La Rioja, Spain) for a PhD grant. I.P.L., S.P-H., R.T. and J.G.P. are part of the European Cooperation in Science and Technology COST Action BM1201, Developmental Origins of Chronic Lung Disease. This work was supported by grants from the Fundación Rioja Salud (Gobierno de La Rioja, Spain) to J.G.P.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Epithelium
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Epithelium
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Epithelial Cells
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Epithelium
                Epithelial Cells
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Epithelium
                Epithelial Cells
                Biology and Life Sciences
                Anatomy
                Respiratory System
                Bronchioles
                Medicine and Health Sciences
                Anatomy
                Respiratory System
                Bronchioles
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Naphthalenes
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Naphthalenes
                Biology and Life Sciences
                Developmental Biology
                Organism Development
                Organogenesis
                Lung Development
                Biology and Life Sciences
                Genetics
                Gene Expression
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Staining
                Cell Staining
                Biology and Life Sciences
                Developmental Biology
                Cell Differentiation
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article