IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other h...

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Autores: Celaya, AM, Rodriguez-De la Rosa, L, Bermudez-Munoz, JM, Zubeldia, JM, Roma-Mateo, C, Avendano, C, Pallardo, FV, Varela-Nieto, I
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p15841
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/15841
Access Level:acceso abierto
Palabra clave:AKT
ARHL
IL1ß
JNK
NIHL
TGFß1
apoptosis
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spelling IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.Celaya, AMRodriguez-De la Rosa, LBermudez-Munoz, JMZubeldia, JMRoma-Mateo, CAvendano, CPallardo, FVVarela-Nieto, IAKTARHLIL1ßJNKNIHLTGFß1apoptosisInsulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1(+/-) mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/15841CellsISSN: 20734409reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p158412026-06-07T16:35:31Z
dc.title.none.fl_str_mv IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
title IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
spellingShingle IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
Celaya, AM
AKT
ARHL
IL1ß
JNK
NIHL
TGFß1
apoptosis
title_short IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
title_full IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
title_fullStr IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
title_full_unstemmed IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
title_sort IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss.
dc.creator.none.fl_str_mv Celaya, AM
Rodriguez-De la Rosa, L
Bermudez-Munoz, JM
Zubeldia, JM
Roma-Mateo, C
Avendano, C
Pallardo, FV
Varela-Nieto, I
author Celaya, AM
author_facet Celaya, AM
Rodriguez-De la Rosa, L
Bermudez-Munoz, JM
Zubeldia, JM
Roma-Mateo, C
Avendano, C
Pallardo, FV
Varela-Nieto, I
author_role author
author2 Rodriguez-De la Rosa, L
Bermudez-Munoz, JM
Zubeldia, JM
Roma-Mateo, C
Avendano, C
Pallardo, FV
Varela-Nieto, I
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AKT
ARHL
IL1ß
JNK
NIHL
TGFß1
apoptosis
topic AKT
ARHL
IL1ß
JNK
NIHL
TGFß1
apoptosis
description Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1(+/-) mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/15841
url https://incliva.portalinvestigacion.com/publicaciones/15841
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cells
ISSN: 20734409
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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