目的:Sox2在组织稳态和再生中起着至关重要的作用。然而,缺乏对Sox2表达及其在颌下腺再生中的功能作用的全面检查。因此,我们旨在阐明Sox2对颌下腺再生的影响。
方法:本研究采用Sprague-Dawley大鼠颌下腺导管结扎/解除结扎再生模型。将Sox2-shRNA载体经导管后施用于颌下腺以建立稳定的Sox2敲低模型。使用常规的组织病理学和分子生物学方法来研究表型变化。
结果:下颌下腺在去除结扎后28天(导管结扎后7天)完全恢复正常。去除结扎后,AQP5表达逐渐增加,直至恢复正常水平。在颌下腺再生中,Sox2与AQP5+腺泡细胞重新表达和共表达,Sox2表达在第14天达到峰值,在第28天恢复正常,再现了发育模式。Sox2敲低阻碍腺体再生并诱导不可逆的纤维化。AQP5表达显著低于同期单独结扎组,而蓝色胶原沉积和波形蛋白表达显著增加。CD68、IL-1β的表达,TNF-α和IL-17A显著升高,Sox2敲除组上皮细胞表达较高水平的IL-17A。
结论:这些发现强调了Sox2作为腺泡细胞谱系的关键调节因子。Sox2+祖细胞是维持腺泡细胞的关键,这对于颌下腺的再生是不可缺少的。总的来说,我们的研究结果可能有助于开发有针对性的干预措施,以增强涎腺疾病的组织修复和预防不可逆的纤维化.
OBJECTIVE: Sox2 plays crucial roles in tissues homeostasis and regeneration. However, there are lack of a comprehensive examination of Sox2 expression and its functional role in submandibular gland regeneration. Therefore, we aimed to elucidate the impact of Sox2 on submandibular gland regeneration.
METHODS: A Sprague-Dawley rat submandibular gland duct ligation/de-ligation regeneration model was conducted in this study. Sox2-shRNA vectors were retro-ductally administered into the submandibular gland to establish a stable Sox2 knockdown model. Conventional histopathological and molecular biological methods were used to investigate phenotypic changes.
RESULTS: The submandibular gland normalized completely 28 days after ligature removal (following 7 days of duct ligation). AQP5 expression gradually increased after ligation removal until returning to normal levels. In submandibular gland regeneration, Sox2 re-expressed and co-expressed with AQP5+ acinar cells, and Sox2 expression peaked on day 14, recovered to normal on day 28, reproducing the developmental pattern. Sox2 knockdown hindered gland regeneration and induced irreversible fibrosis. The AQP5 expression was significantly lower than the contemporaneous solely ligated group, while the blue collagen deposition and the Vimentin expression increased prominently. The expression of CD68, IL-1β, TNF-α and IL-17A increased significantly, and epithelial cells in the Sox2 knockdown group expressed higher levels of IL-17A.
CONCLUSIONS: These findings highlight Sox2 as a crucial regulator of the acinar cell lineage. Sox2+ progenitor cells are pivotal for acinar cell maintenance, which is indispensable for submandibular gland regeneration. Collectively, our findings may help develop targeted interventions for enhancing tissue repair and preventing irreversible fibrosis in salivary gland disorders.