Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss
Background: It has been reported the therapeutic effects of mesenchymal stem cells (MSCs) on hearing loss. This study explored the therapeutic effects of growth differentiation factor 6 (GDF6) overexpression-induced MSCs (MSCs-GDF6) on age-related hearing loss (ARHL) and its under...
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IMR Press
2025-01-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL26179 |
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| author | Jiali Liu Haisen Peng Yuehui Liu Chunhua Li Wen Xie |
| author_facet | Jiali Liu Haisen Peng Yuehui Liu Chunhua Li Wen Xie |
| author_sort | Jiali Liu |
| collection | DOAJ |
| description | Background: It has been reported the therapeutic effects of mesenchymal stem cells (MSCs) on hearing loss. This study explored the therapeutic effects of growth differentiation factor 6 (GDF6) overexpression-induced MSCs (MSCs-GDF6) on age-related hearing loss (ARHL) and its underlying mechanisms. Methods: Reverse transcription-quantitative PCR and western blotting were used to evaluate gene expression. Flow cytometry and immunofluorescence assays were performed for the detection of apoptosis and autophagy, respectively. Hearing function and loss of outer hair cells (HCs) in ARHL rats were measured using the auditory brainstem response and cochlear silver nitrate staining, respectively. MSC proliferation was evaluated with the Cell Counting Kit-8 assay. Results: Growth differentiation factor 15 (GDF15) and sirtuin 1 (SIRT1) expression was significantly decreased in hydrogen peroxide (H2O2)-induced House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and the cochlea of ARHL rats. Elevated apoptosis and blocked autophagic flux were uncovered in H2O2-induced HEI-OC1 cells and ARHL rats. GDF15 overexpression inhibited apoptosis and restored autophagic flux in vitro and in vivo. Meanwhile, GDF15 positively regulated SIRT1 protein expression. MSCs-GDF6 not only upregulated GDF15 and SIRT1 expression but also suppressed apoptosis and restored autophagic flux to reduce loss of HCs and hearing loss in ARHL rats. Conclusions: MSCs-GDF6 prevented loss of HCs to relieve ARHL by inhibiting apoptosis and restoring autophagic flux, likely in association with upregulation of the GDF15/SIRT1 axis. |
| format | Article |
| id | doaj-art-54d47ca8cffc412da804801390527199 |
| institution | Kabale University |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-54d47ca8cffc412da8048013905271992025-01-25T08:55:53ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-01-013012617910.31083/FBL26179S2768-6701(24)01600-9Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing LossJiali Liu0Haisen Peng1Yuehui Liu2Chunhua Li3Wen Xie4Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, ChinaDepartment of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, ChinaDepartment of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, ChinaDepartment of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, ChinaDepartment of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, ChinaBackground: It has been reported the therapeutic effects of mesenchymal stem cells (MSCs) on hearing loss. This study explored the therapeutic effects of growth differentiation factor 6 (GDF6) overexpression-induced MSCs (MSCs-GDF6) on age-related hearing loss (ARHL) and its underlying mechanisms. Methods: Reverse transcription-quantitative PCR and western blotting were used to evaluate gene expression. Flow cytometry and immunofluorescence assays were performed for the detection of apoptosis and autophagy, respectively. Hearing function and loss of outer hair cells (HCs) in ARHL rats were measured using the auditory brainstem response and cochlear silver nitrate staining, respectively. MSC proliferation was evaluated with the Cell Counting Kit-8 assay. Results: Growth differentiation factor 15 (GDF15) and sirtuin 1 (SIRT1) expression was significantly decreased in hydrogen peroxide (H2O2)-induced House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and the cochlea of ARHL rats. Elevated apoptosis and blocked autophagic flux were uncovered in H2O2-induced HEI-OC1 cells and ARHL rats. GDF15 overexpression inhibited apoptosis and restored autophagic flux in vitro and in vivo. Meanwhile, GDF15 positively regulated SIRT1 protein expression. MSCs-GDF6 not only upregulated GDF15 and SIRT1 expression but also suppressed apoptosis and restored autophagic flux to reduce loss of HCs and hearing loss in ARHL rats. Conclusions: MSCs-GDF6 prevented loss of HCs to relieve ARHL by inhibiting apoptosis and restoring autophagic flux, likely in association with upregulation of the GDF15/SIRT1 axis.https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL26179mesenchymal stem cellsgdf15sirt1cochlear hair cellage-related hearing loss |
| spellingShingle | Jiali Liu Haisen Peng Yuehui Liu Chunhua Li Wen Xie Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss Frontiers in Bioscience-Landmark mesenchymal stem cells gdf15 sirt1 cochlear hair cell age-related hearing loss |
| title | Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss |
| title_full | Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss |
| title_fullStr | Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss |
| title_full_unstemmed | Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss |
| title_short | Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss |
| title_sort | therapeutic effects of gdf6 overexpressing mesenchymal stem cells through upregulation of the gdf15 sirt1 axis in age related hearing loss |
| topic | mesenchymal stem cells gdf15 sirt1 cochlear hair cell age-related hearing loss |
| url | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL26179 |
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