Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway
Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8356 |
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| author | Anqi Sun Huijing Ye Zhihui Xu Jingqiao Chen Wei Xiao Te Zhang Xiaotong Sha Shaowei Bi Tianyi Zhou Huasheng Yang |
| author_facet | Anqi Sun Huijing Ye Zhihui Xu Jingqiao Chen Wei Xiao Te Zhang Xiaotong Sha Shaowei Bi Tianyi Zhou Huasheng Yang |
| author_sort | Anqi Sun |
| collection | DOAJ |
| description | Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software. Additionally, the RNA sequencing results were validated by quantitative real-time polymerase chain reaction (qRT–PCR). Bioinformatic prediction identified the functions of differentially expressed genes (DEGs). Further orbital connective tissue and serum samples of the TAO and control groups were collected for subsequent experiments. Histologic staining, Western blotting (WB), qRT–PCR, enzyme-linked immunosorbent assays (ELISAs), gene overexpression through lentiviral infection or silencing gene by short interfering RNA (siRNA) were performed. We found that the relaxin signaling pathway is an important regulatory pathway in TAO fibrosis pathogenesis. Serelaxin exerts antifibrotic and anti-inflammatory effects in TAO. Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1. |
| first_indexed | 2024-03-11T04:16:37Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:37Z |
| publishDate | 2023-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e1425345e1084bc8bec9848da90cce612023-11-17T23:08:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249835610.3390/ijms24098356Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch PathwayAnqi Sun0Huijing Ye1Zhihui Xu2Jingqiao Chen3Wei Xiao4Te Zhang5Xiaotong Sha6Shaowei Bi7Tianyi Zhou8Huasheng Yang9State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, ChinaFibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software. Additionally, the RNA sequencing results were validated by quantitative real-time polymerase chain reaction (qRT–PCR). Bioinformatic prediction identified the functions of differentially expressed genes (DEGs). Further orbital connective tissue and serum samples of the TAO and control groups were collected for subsequent experiments. Histologic staining, Western blotting (WB), qRT–PCR, enzyme-linked immunosorbent assays (ELISAs), gene overexpression through lentiviral infection or silencing gene by short interfering RNA (siRNA) were performed. We found that the relaxin signaling pathway is an important regulatory pathway in TAO fibrosis pathogenesis. Serelaxin exerts antifibrotic and anti-inflammatory effects in TAO. Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1.https://www.mdpi.com/1422-0067/24/9/8356thyroid-associated ophthalmopathyfibrosisserelaxinRXFP1Notch signaling pathway |
| spellingShingle | Anqi Sun Huijing Ye Zhihui Xu Jingqiao Chen Wei Xiao Te Zhang Xiaotong Sha Shaowei Bi Tianyi Zhou Huasheng Yang Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway International Journal of Molecular Sciences thyroid-associated ophthalmopathy fibrosis serelaxin RXFP1 Notch signaling pathway |
| title | Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway |
| title_full | Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway |
| title_fullStr | Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway |
| title_full_unstemmed | Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway |
| title_short | Serelaxin Alleviates Fibrosis in Thyroid-Associated Ophthalmopathy via the Notch Pathway |
| title_sort | serelaxin alleviates fibrosis in thyroid associated ophthalmopathy via the notch pathway |
| topic | thyroid-associated ophthalmopathy fibrosis serelaxin RXFP1 Notch signaling pathway |
| url | https://www.mdpi.com/1422-0067/24/9/8356 |
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