Col1a1 mediates the focal adhesion pathway affecting hearing in miR-29a mouse model by RNA-seq analysis
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
Age-related hearing loss (ARHL) is a common neurodegenerative disease. Its molecular mechanisms have not been fully elucidated. In the present study, we obtained differential mRNA expression in the cochlea of 2-month-old miR-29a+/+ mice and miR-29a-/- mice by RNA-seq. Gene ontology (GO) analysis was used to identify molecular functions associated with hearing in miR-29a-/- mice, including being actin binding (GO: 0003779) and immune processes. We focused on the intersection of differential genes, miR-29a target genes and the sensory perception of sound (GO:0007605) genes, with six mRNA at this intersection, and we selected Col1a1 as our target gene. We validated Col1a1 as the direct target of miR-29a by molecular and cellular experiments. Total 6 pathways involved in Col1a1 were identified by through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We selected the focal adhesion pathway as our target pathway based. Their expression levels in miR-29a-/- mice were verified by qRT-PCR and Western blot. Compared with miR-29a+/+ mice, the expression levels of Col1a1, Itga4, Itga2, Itgb3, Itgb7, Pik3r3 and Ptk2 were different in miR-29a-/- mice. Immunofluorescence was used to locate genes in the cochlea. Col1a1, Itga4 and Itgb3 were differentially expressed in the basilar membranes and stria vascularis and spiral ganglion neurons compared to miR-29a+/+ mice. Pik3r3 and Ptk2 were differentially expressed in the basilar membranes and stria vascularis, but not at the s spiral ganglion neurons compared to miR-29a+/+ mice. Our results show that when miR-29a is knocked out, the Col1a1 mediates the focal adhesion pathway may affect the hearing of miR-29a-/- mice. These findings may provide a new direction for effective treatment of age-related hearing loss.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:185 |
|---|---|
| Enthalten in: |
Experimental gerontology - 185(2024) vom: 15. Jan., Seite 112349 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Shuli [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Age-related hearing loss |
|---|
| Anmerkungen: |
Date Completed 10.01.2024 Date Revised 21.01.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.exger.2023.112349 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36594503X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36594503X | ||
| 003 | DE-627 | ||
| 005 | 20240121231908.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231227s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.exger.2023.112349 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1266.xml |
| 035 | |a (DE-627)NLM36594503X | ||
| 035 | |a (NLM)38103809 | ||
| 035 | |a (PII)S0531-5565(23)00270-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Shuli |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Col1a1 mediates the focal adhesion pathway affecting hearing in miR-29a mouse model by RNA-seq analysis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.01.2024 | ||
| 500 | |a Date Revised 21.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Age-related hearing loss (ARHL) is a common neurodegenerative disease. Its molecular mechanisms have not been fully elucidated. In the present study, we obtained differential mRNA expression in the cochlea of 2-month-old miR-29a+/+ mice and miR-29a-/- mice by RNA-seq. Gene ontology (GO) analysis was used to identify molecular functions associated with hearing in miR-29a-/- mice, including being actin binding (GO: 0003779) and immune processes. We focused on the intersection of differential genes, miR-29a target genes and the sensory perception of sound (GO:0007605) genes, with six mRNA at this intersection, and we selected Col1a1 as our target gene. We validated Col1a1 as the direct target of miR-29a by molecular and cellular experiments. Total 6 pathways involved in Col1a1 were identified by through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We selected the focal adhesion pathway as our target pathway based. Their expression levels in miR-29a-/- mice were verified by qRT-PCR and Western blot. Compared with miR-29a+/+ mice, the expression levels of Col1a1, Itga4, Itga2, Itgb3, Itgb7, Pik3r3 and Ptk2 were different in miR-29a-/- mice. Immunofluorescence was used to locate genes in the cochlea. Col1a1, Itga4 and Itgb3 were differentially expressed in the basilar membranes and stria vascularis and spiral ganglion neurons compared to miR-29a+/+ mice. Pik3r3 and Ptk2 were differentially expressed in the basilar membranes and stria vascularis, but not at the s spiral ganglion neurons compared to miR-29a+/+ mice. Our results show that when miR-29a is knocked out, the Col1a1 mediates the focal adhesion pathway may affect the hearing of miR-29a-/- mice. These findings may provide a new direction for effective treatment of age-related hearing loss | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Age-related hearing loss | |
| 650 | 4 | |a Col1a1 | |
| 650 | 4 | |a Focal adhesion pathway | |
| 650 | 4 | |a RNA-seq | |
| 650 | 4 | |a miR-29a | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a MIRN29a microRNA, mouse |2 NLM | |
| 650 | 7 | |a COL1A1 protein, human |2 NLM | |
| 700 | 1 | |a Li, Mulan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Pengcheng |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Yaning |e verfasserin |4 aut | |
| 700 | 1 | |a Geng, Ruishuang |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Tihua |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Qingyin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Peng |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Experimental gerontology |d 1968 |g 185(2024) vom: 15. Jan., Seite 112349 |w (DE-627)NLM000016608 |x 1873-6815 |7 nnns |
| 773 | 1 | 8 | |g volume:185 |g year:2024 |g day:15 |g month:01 |g pages:112349 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.exger.2023.112349 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 185 |j 2024 |b 15 |c 01 |h 112349 | ||