Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model
Purpose. Slc26a4-/- mice exhibit severer defects in the development of the cochlea and develop deafness, while the underlying mechanisms responsible for these effects remain unclear. Our study was to investigate the potential mechanism linking SLC26A4 deficiency to hearing loss. Materials and Method...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2021/5585394 |
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| author | Wenyue Xue Yuxin Tian Yuanping Xiong Feng Liu Yanmei Feng Zhengnong Chen Dongzhen Yu Shankai Yin |
| author_facet | Wenyue Xue Yuxin Tian Yuanping Xiong Feng Liu Yanmei Feng Zhengnong Chen Dongzhen Yu Shankai Yin |
| author_sort | Wenyue Xue |
| collection | DOAJ |
| description | Purpose. Slc26a4-/- mice exhibit severer defects in the development of the cochlea and develop deafness, while the underlying mechanisms responsible for these effects remain unclear. Our study was to investigate the potential mechanism linking SLC26A4 deficiency to hearing loss. Materials and Methods. RNA sequencing was applied to analyze the differential gene expression of the stria vascularis (SV) from wildtype and Slc26a4-/- mice. GO and KEGG pathway analysis were performed. Quantitative RT-PCR was applied to validate the expression of candidate genes affected by Slc26a4. ELISA and immunofluorescence technique were used to detect the homocysteine (Hcy) level in serum, brain, and SV, respectively. Results. 183 upregulated genes and 63 downregulated genes were identified in the SV associated with Slc26a4 depletion. Transcriptomic profiling revealed that Slc26a4 deficiency significantly affected the expression of genes associated with cell adhesion, transmembrane transport, and the biogenesis of multicellular organisms. The SV from Slc26a4-/- mice exhibited a higher expression of Bhmt mRNAs, as well as altered homocysteine (Hcy) metabolism. Conclusions. The altered expression of Bhmt results in a dramatic change in multiple biochemical reactions and a disruption of nutrient homeostasis in the endolymph which may contribute to hearing loss of Slc26a4 knockout mouse. |
| format | Article |
| id | doaj-art-4426f7126a4148c7916d3b523dbb3542 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-4426f7126a4148c7916d3b523dbb35422025-02-03T01:20:38ZengWileyNeural Plasticity2090-59041687-54432021-01-01202110.1155/2021/55853945585394Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse ModelWenyue Xue0Yuxin Tian1Yuanping Xiong2Feng Liu3Yanmei Feng4Zhengnong Chen5Dongzhen Yu6Shankai Yin7Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaPurpose. Slc26a4-/- mice exhibit severer defects in the development of the cochlea and develop deafness, while the underlying mechanisms responsible for these effects remain unclear. Our study was to investigate the potential mechanism linking SLC26A4 deficiency to hearing loss. Materials and Methods. RNA sequencing was applied to analyze the differential gene expression of the stria vascularis (SV) from wildtype and Slc26a4-/- mice. GO and KEGG pathway analysis were performed. Quantitative RT-PCR was applied to validate the expression of candidate genes affected by Slc26a4. ELISA and immunofluorescence technique were used to detect the homocysteine (Hcy) level in serum, brain, and SV, respectively. Results. 183 upregulated genes and 63 downregulated genes were identified in the SV associated with Slc26a4 depletion. Transcriptomic profiling revealed that Slc26a4 deficiency significantly affected the expression of genes associated with cell adhesion, transmembrane transport, and the biogenesis of multicellular organisms. The SV from Slc26a4-/- mice exhibited a higher expression of Bhmt mRNAs, as well as altered homocysteine (Hcy) metabolism. Conclusions. The altered expression of Bhmt results in a dramatic change in multiple biochemical reactions and a disruption of nutrient homeostasis in the endolymph which may contribute to hearing loss of Slc26a4 knockout mouse.http://dx.doi.org/10.1155/2021/5585394 |
| spellingShingle | Wenyue Xue Yuxin Tian Yuanping Xiong Feng Liu Yanmei Feng Zhengnong Chen Dongzhen Yu Shankai Yin Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model Neural Plasticity |
| title | Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model |
| title_full | Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model |
| title_fullStr | Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model |
| title_full_unstemmed | Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model |
| title_short | Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model |
| title_sort | transcriptomic analysis reveals an altered hcy metabolism in the stria vascularis of the pendred syndrome mouse model |
| url | http://dx.doi.org/10.1155/2021/5585394 |
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