Salivary Gland Secretion Mechanisms During Normal and Altered Functional States

正常和改变功能状态下的唾液腺分泌机制

• 批准号: 6432003
• 负责人: BRUCE J BAUM
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432003
• 关键词: Adenoviridae; acinar cell; epithelium; gene therapy; laboratory rat; recombinant virus; saliva; salivary disorder; salivary glands; salivation; tissue /cell culture; transfection; water channel

The health of the oral cavity is maintained by salivary secretions. Our past studies focused on understanding mechanisms of saliva formation, their alteration during pathology, and developing novel methods to treat salivary dysfunction. During this reporting period we continued to utilize gene transfer technology to alter salivary epithelial cells to address clinical and biological questions. We have extended studies using adeno-associated viral vectors (serotype 2), demonstrating stable expression in, and transgene product secretion from, murine submandibular glands (SMGs) for >2 months. We also continued our studies on the hybrid adeno-retroviral vector that we reported last year, focusing on understanding the mechanism of genomic integration achieved. We previously showed that transgenes contain sorting signals recognized by salivary glands in vivo, leading to specific patterns of polarized protein secretion. Our focus this year was on the manipulation these secretory patterns to enhance endocrine-like secretion. We continued our studies on aquaporin water channels associated with salivary secretion and showed that AQP8 is localized to the basolateral membranes of rat SMGs. We also continued to make progress towards the development of an orally implantable, first generation artificial salivary gland. Our clinical studies continue to focus on determining if the salivary dysfunction accompanying Sjogren's syndrome can be ameliorated by immunomodulatory therapy.

口腔的健康是由唾液分泌物维持的。 我们过去的研究集中在理解唾液形成的机制，病理学期间的改变以及开发用于治疗唾液功能障碍的新方法。在此报告期间，我们继续利用基因转移技术改变唾液上皮细胞来解决临床和生物学问题。我们使用腺相关的病毒载体（血清型2）进行了扩展研究，表明鼠类下颌腺（SMG）中的稳定表达和转基因产物分泌> 2个月。我们还继续对去年报道的混合腺病毒载体进行研究，重点是理解基因组整合的机理。我们先前表明，转基因含有体内唾液腺识别的分类信号，从而导致了极化蛋白质分泌的特定模式。我们今年的重点是这些分泌模式的操纵以增强内分泌样分泌。我们继续研究与唾液分泌有关的水通道水通道，并表明AQP8位于大鼠SMG的基底外侧膜。我们还继续朝着开发口服的，第一代人造唾液腺的发展。我们的临床研究继续专注于确定伴随Sjogren综合征的唾液功能障碍是否可以通过免疫调节治疗来改善。