Substance P/neurokinin-1 receptor pathway blockade ameliorates limbal stem cell deficiency by modulating mTOR pathway and preventing cell senescence.

Cellular Senescence Corneal Diseases / metabolism Epithelium, Corneal Humans Limbus Corneae / metabolism Receptors, Neurokinin-1 / genetics Stem Cells Substance P / metabolism TOR Serine-Threonine Kinases / metabolism
corneal wound healing mammalian target of rapamycin neurokinin-1 receptor antagonist stem cell deficiency substance P

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
12 04 2022
Historique:
received: 06 05 2021
revised: 18 02 2022
accepted: 21 02 2022
pubmed: 26 3 2022
medline: 16 4 2022
entrez: 25 3 2022
Statut: ppublish

Résumé

Severe ocular surface diseases can lead to limbal stem cell deficiency (LSCD), which is accompanied by defective healing. We aimed to evaluate the role of the substance P (SP)/neurokinin-1 receptor (NK1R) pathway in corneal epithelium wound healing in a pre-clinical model of LSCD. SP ablation or NK1R blockade significantly increased epithelial wound healing (p < 0.001) and corneal transparency (p < 0.001), compared with wild type (WT). In addition, a reduced number of infiltrating goblet and conjunctival cells (p < 0.05) and increased number of epithelial stem cells (p < 0.01), which also expressed NK1R, was observed. The mammalian target of rapamycin (mTOR) pathway was significantly inhibited (p < 0.05) and expression of γH2AX was significantly reduced (p < 0.05) after SP ablation. These results suggest that excessive expression of SP is associated with LSCD and results in accelerated senescence and exhaustion of residual stem cells. Topical treatment with NK1R antagonist ameliorates clinical signs associated with LSCD and could be used as an adjuvant treatment in LSCD.

Identifiants

DOI: 10.1016/j.stemcr.2022.02.012 PMID: 35334220 PMC: PMC9023781
pubmed: 35334220
pii: S2213-6711(22)00101-1
doi: 10.1016/j.stemcr.2022.02.012
pmc: PMC9023781
pii:
doi:

Substances chimiques

Receptors, Neurokinin-1 0
Substance P 33507-63-0
MTOR protein, human EC 2.7.1.1
TOR Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

849-863

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Romina Lasagni Vitar (R)

Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

Francesca Triani (F)

Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

Marco Barbariga (M)

Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

Philippe Fonteyne (P)

Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

Paolo Rama (P)

Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

Giulio Ferrari (G)

Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. Electronic address: ferrari.giulio@hsr.it.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Vieillissement de la cellule › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Maladies de l'oeil › Maladies de la cornée › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Tissus › Épithélium › Épithélium antérieur de la cornée › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Organes des sens › Oeil › Pôle antérieur du bulbe oculaire › Cornée › Limbe de la cornée › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur aux neuropeptides › Récepteur tachykinine › Récepteur de la neurokinine 1 › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Cellules › Cellules souches › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Kinines › Tachykinines › Substance P › Substance P/neurokinin-1 receptor pathway...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Substance P/neurokinin-1 receptor pathway...