SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadias
Abstract The transcription factor SOX9 is crucial in the development and differentiation of various tissues and cells. However, the roles of SOX9‐dependent genes and pathways in normal urethral development and the mechanism of hypospadias are unclear. This study collected 15 foreskin tissue specimen...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Pediatric Discovery |
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| Online Access: | https://doi.org/10.1002/pdi3.94 |
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| _version_ | 1849219955457785856 |
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| author | Xueyu He Zhicheng Zhang Zhenmin Liu Qiang Zhang Chunlan Long Lianju Shen Guanghui Wei Xing Liu |
| author_facet | Xueyu He Zhicheng Zhang Zhenmin Liu Qiang Zhang Chunlan Long Lianju Shen Guanghui Wei Xing Liu |
| author_sort | Xueyu He |
| collection | DOAJ |
| description | Abstract The transcription factor SOX9 is crucial in the development and differentiation of various tissues and cells. However, the roles of SOX9‐dependent genes and pathways in normal urethral development and the mechanism of hypospadias are unclear. This study collected 15 foreskin tissue specimens from patients who underwent hypospadias repair surgery and compared them to normal foreskin tissue specimens obtained during circumcision. The expression levels of SOX9, WNT signaling pathway markers, and epithelial‐mesenchymal transition (EMT) markers were analyzed in both groups. It was found that mRNA and protein levels of SOX9, WNT signaling pathway, and EMT mesenchymal markers were significantly reduced in the hypospadias group compared to the normal foreskin group. In contrast, mRNA and protein levels of epithelial markers were significantly increased in the hypospadias group. Immunofluorescence confirmed the decrease in SOX9 expression. Experiments using siRNA to inhibit SOX9 expression in foreskin fibroblasts yielded similar results to the hypospadias group. The findings suggest that down‐regulation of SOX9 expression may contribute to the development of hypospadias by down‐regulating the WNT pathway and inhibiting EMT. These findings provide new insights into the embryonic development of the urethra. |
| format | Article |
| id | doaj-art-beac2c84a43e45649af9d634ec51b087 |
| institution | Kabale University |
| issn | 2835-558X 2835-5598 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pediatric Discovery |
| spelling | doaj-art-beac2c84a43e45649af9d634ec51b0872024-12-25T02:21:42ZengWileyPediatric Discovery2835-558X2835-55982024-12-0124n/an/a10.1002/pdi3.94SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadiasXueyu He0Zhicheng Zhang1Zhenmin Liu2Qiang Zhang3Chunlan Long4Lianju Shen5Guanghui Wei6Xing Liu7Department of Urology Children's Hospital of Chongqing Medical University Chongqing ChinaDepartment of Urology Children's Hospital of Chongqing Medical University Chongqing ChinaDepartment of Urology Children's Hospital of Chongqing Medical University Chongqing ChinaDepartment of Urology Children's Hospital of Chongqing Medical University Chongqing ChinaNational Clinical Research Center for Child Health and Disorders Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical University Chongqing ChinaNational Clinical Research Center for Child Health and Disorders Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical University Chongqing ChinaDepartment of Urology Children's Hospital of Chongqing Medical University Chongqing ChinaDepartment of Urology Children's Hospital of Chongqing Medical University Chongqing ChinaAbstract The transcription factor SOX9 is crucial in the development and differentiation of various tissues and cells. However, the roles of SOX9‐dependent genes and pathways in normal urethral development and the mechanism of hypospadias are unclear. This study collected 15 foreskin tissue specimens from patients who underwent hypospadias repair surgery and compared them to normal foreskin tissue specimens obtained during circumcision. The expression levels of SOX9, WNT signaling pathway markers, and epithelial‐mesenchymal transition (EMT) markers were analyzed in both groups. It was found that mRNA and protein levels of SOX9, WNT signaling pathway, and EMT mesenchymal markers were significantly reduced in the hypospadias group compared to the normal foreskin group. In contrast, mRNA and protein levels of epithelial markers were significantly increased in the hypospadias group. Immunofluorescence confirmed the decrease in SOX9 expression. Experiments using siRNA to inhibit SOX9 expression in foreskin fibroblasts yielded similar results to the hypospadias group. The findings suggest that down‐regulation of SOX9 expression may contribute to the development of hypospadias by down‐regulating the WNT pathway and inhibiting EMT. These findings provide new insights into the embryonic development of the urethra.https://doi.org/10.1002/pdi3.94epithelial‐mesenchymal transformationhypospadiasSOX9WNT/β‐catenin |
| spellingShingle | Xueyu He Zhicheng Zhang Zhenmin Liu Qiang Zhang Chunlan Long Lianju Shen Guanghui Wei Xing Liu SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadias Pediatric Discovery epithelial‐mesenchymal transformation hypospadias SOX9 WNT/β‐catenin |
| title | SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadias |
| title_full | SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadias |
| title_fullStr | SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadias |
| title_full_unstemmed | SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadias |
| title_short | SOX9 regulates epithelial‐mesenchymal transformation by mediating the Wnt/β‐catenin signaling pathway in hypospadias |
| title_sort | sox9 regulates epithelial mesenchymal transformation by mediating the wnt β catenin signaling pathway in hypospadias |
| topic | epithelial‐mesenchymal transformation hypospadias SOX9 WNT/β‐catenin |
| url | https://doi.org/10.1002/pdi3.94 |
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