RESUMO
In mammalian cells, Smad2 and Smad3, two receptor-regulated Smad proteins, play crucial roles in the signal transmission of transforming growth factor-ß (TGF-ß) and are involved in various cell regulatory processes, including epithelial-mesenchymal transition-associated cell responses, that is, cell morphological changes, E-cadherin downregulation, stress fiber formation, and cell motility enhancement. Smad2 contains an additional exon encoding 30 amino acid residues compared with Smad3, leading to distinct Smad2 and Smad3 functional properties. Intriguingly, Smad2 also has an alternatively spliced isoform termed Smad2Δexon3 (also known as Smad2ß) lacking the additional exon and behaving similarly to Smad3. However, Smad2Δexon3 and Smad3 signaling properties have not yet been compared in detail. In this study, we reveal that Smad2Δexon3 rescues multiple TGF-ß-induced in vitro cellular responses that would become defective upon SMAD3 KO but does not rescue cell motility enhancement. Using Smad2Δexon3/Smad3 chimeric proteins, we identified that residues Arg-104 and Asn-210 in Smad3, which are not conserved in Smad2Δexon3, are key for TGF-ß-enhanced cell motility. Moreover, we discovered that Smad2Δexon3 fails to rescue the enhanced cell motility as it does not mediate TGF-ß signals to downregulate transcription of ARHGAP24, a GTPase-activating protein that targets Rac1. This study reports for the first time distinct signaling properties of Smad2Δexon3 and Smad3.
Assuntos
Movimento Celular , Éxons , Deleção de Sequência , Transdução de Sinais , Proteína Smad2 , Proteína Smad3 , Fator de Crescimento Transformador beta , Animais , Mamíferos/metabolismo , Proteína Smad2/química , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/deficiência , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Éxons/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismoRESUMO
Purpose Postoperative pain management methods for tonsillectomy commonly include the use of opioids, non-steroidal anti-inflammatory drugs, and acetaminophen. However, some patients report pain despite the use of these medications. In recent years, ultrasound-guided selective glossopharyngeal nerve block (UGSGNB) and ultrasound-guided maxillary nerve block (UGMNB) have been reported to be effective for analgesia post-tonsillectomy. We retrospectively analyzed the effects of UGSGNB and UGMNB in the perioperative management of patients who underwent tonsillectomy under general anesthesia. Methods This retrospective study evaluated adults (18-61 years old) who had received general anesthesia for tonsillectomy. The control group comprised 25 patients who received general anesthesia using the standard protocol, and the nerve block group comprised 10 patients who also received additional UGGNB and UGMNB. Results While these nerve blocks may have contributed to improving the postoperative food intake, they did not reduce the frequency of postoperative analgesia used. Improved dietary intake after UGSGNB and UGMNB could be advantageous for postoperative recovery. Conclusion Further research with a larger number of cases and prospective intervention studies are necessary to determine the effects of combining UGSGNB and UGMNB for post-tonsillectomy analgesia.