{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:15:42Z","timestamp":1771035342055,"version":"3.50.1"},"reference-count":38,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells Tissues Organs"],"abstract":"<jats:p>Introduction: This study aimed to examine the transforming growth factor (TGF)-\u03b2 signaling pathway during secondary palate fusion by transfecting single and double small interfering RNA (siRNAs) for TGF-\u03b22 and -\u03b23. This investigation also focused on understanding the phenotype of palatal development. Methods: siRNAs targeting TGF-\u03b22 and -\u03b23 were used in an organ culture model of fusion of the secondary palate of 13-day embryonic ICR mice cultured for up to 72 h. The palatal shelves were collected at different times following the initiation of organ culture and were examined for TGF-\u03b22 and -\u03b23 gene expression. Downstream signaling was characterized using Western blotting and PCR. Results: In the double siRNA-treated palatal shelves, approximately 90% (91% anterior, 89% posterior with phenotype A) showed fusion failure in hematoxylin and eosin staining. Phosphorylation of Smad-dependent and -independent signaling showed a significant reduction in phosphorylation in double knockdown palate organ cultures when compared to single knockdown cultures. Although, the expression of matrix metalloproteinase 13 and TIMP2 were small influenced by siTGF-\u03b22, the extracellular matrix and transcription factor expressions showed to be significantly reduced in double knockdown palate compared to single knockdown palates. Conclusions: This study demonstrates that double siRNAs targeting TGF-\u03b22 and -\u03b23 results in phenotypes during secondary palatal fusion and that they could be affected phosphorylation of Smad-dependent and -independent signaling synergistically compared to single knockdown of TGF-\u03b22 and -\u03b23. The results of this study demonstrate important functions during secondary palatal fusion and will contribute to our understanding of the etiology of cleft palate. <\/jats:p>","DOI":"10.1159\/000544097","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T13:01:12Z","timestamp":1742389272000},"page":"351-365","source":"Crossref","is-referenced-by-count":1,"title":["Function of Transforming Growth Factor \u03b22 and \u03b23 in 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