Inhibition of focal adhesion kinase increases adult olfactory stem cell self-renewal and neuroregeneration through ciliary neurotrophic factor.

Animals Cell Self Renewal Ciliary Neurotrophic Factor / genetics Focal Adhesion Protein-Tyrosine Kinases Mice Nerve Regeneration Neurogenesis Olfactory Mucosa
Basal cell proliferation Neuronal differentiation Neuroregeneration Olfactory function Olfactory stem cell

Journal

Stem cell research
ISSN: 1876-7753
Titre abrégé: Stem Cell Res
Pays: England
ID NLM: 101316957

Informations de publication

Date de publication:
12 2020
Historique:
received: 19 06 2020
revised: 12 10 2020
accepted: 20 10 2020
pubmed: 2 11 2020
medline: 22 6 2021
entrez: 1 11 2020
Statut: ppublish

Résumé

Constant neuroregeneration in adult olfactory epithelium maintains olfactory function by basal stem cell proliferation and differentiation to replace lost olfactory sensory neurons (OSNs). Understanding the mechanisms regulating this process could reveal potential therapeutic targets for stimulating adult olfactory neurogenesis under pathological conditions and aging. Ciliary neurotrophic factor (CNTF) in astrocytes promotes forebrain neurogenesis but its function in the olfactory system is unknown. Here, we show in mouse olfactory epithelium that CNTF is expressed in horizontal basal cells, olfactory ensheathing cells (OECs) and a small subpopulation of OSNs. CNTF receptor alpha was expressed in Mash1-positive globose basal cells (GBCs) and OECs. Thus, CNTF may affect GBCs in a paracrine manner. CNTF-/- mice did not display altered GBC proliferation or olfactory function, suggesting that CNTF is not involved in basal olfactory renewal or that they developed compensatory mechanisms. Therefore, we tested the effect of increased CNTF in wild type mice. Intranasal instillation of a focal adhesion kinase (FAK) inhibitor, FAK14, upregulated CNTF expression. FAK14 also promoted GBC proliferation, neuronal differentiation and basal stem cell self-renewal but had no effective in CNTF-/- mice, suggesting that FAK inhibition promotes olfactory neuroregeneration through CNTF, making them potential targets to treat sensorineural anosmia due to OSN loss.

Identifiants

DOI: 10.1016/j.scr.2020.102061 PMID: 33130470 PMC: PMC7903807
pubmed: 33130470
pii: S1873-5061(20)30362-7
doi: 10.1016/j.scr.2020.102061
pmc: PMC7903807
mid: NIHMS1658027
pii:
doi:

Substances chimiques

Ciliary Neurotrophic Factor 0
Focal Adhesion Protein-Tyrosine Kinases EC 2.7.10.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

102061

Subventions

Organisme : NCRR NIH HHS
ID : C06 RR030651
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG029493
Pays : United States

Informations de copyright

Published by Elsevier B.V.

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Auteurs

Cuihong Jia (C)

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States. Electronic address: jiac01@etsu.edu.

Joe Oliver (J)

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.

Dustin Gilmer (D)

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.

Chiharu Lovins (C)

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.

Diego J Rodriguez-Gil (DJ)

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.

Theo Hagg (T)

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Inhibition of focal adhesion kinase increases...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Division cellulaire › Auto-renouvellement cellulaire › Inhibition of focal adhesion kinase increases...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance nerveuse › Facteur neurotrophique ciliaire › Inhibition of focal adhesion kinase increases...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Focal adhesion protein-tyrosine kinases › Inhibition of focal adhesion kinase increases...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Inhibition of focal adhesion kinase increases...
questionsmedicales.fr › Phénomènes biologiques › Régénération › Régénération nerveuse › Inhibition of focal adhesion kinase increases...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Neurogenèse › Inhibition of focal adhesion kinase increases...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse respiratoire › Muqueuse nasale › Muqueuse olfactive › Inhibition of focal adhesion kinase increases...