Salivary Gland Secretion Mechanisms

唾液腺分泌机制

• 批准号: 6501168
• 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/6501168
• 关键词: Adenoviridae; Sjogren's syndrome; adeno associated virus group; biomimetics; chloroquine; epithelium; gastrointestinal pharmacology; gene therapy; genetically modified animals; human subject; human therapy evaluation; immunomodulators; immunotherapy; interleukin 10; laboratory rat; patient oriented research; prosthesis; radiobiology; salivary disorder; salivary glands; salivation; secretion; somatotropin; transfection; transfection /expression vector

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 of biologically active human IL-10 in, and 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 if the integrated transgene is the site of expression. We previously showed that transgenes contain sorting signals recognized by salivary glands in vivo, leading to specific patterns of polarized protein secretion. This year we showed that the use of hydroxychloroquine facilitates the endocrine-like secretion transgenic human growth hormone from salivary glands. 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, and our results this year provide support for this hypothesis.

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。我们使用腺相关病毒载体（血清型2）进行了扩展研究，表明生物活性人体IL-10 IN的表达稳定，以及鼠类下颌下腺（SMG）的分泌> 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，重点是了解综合转基因是否是表达的位点。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。今年我们表明，羟氯喹的使用促进了唾液腺中内分泌样的转基因人类生长激素。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Sjogren综合征伴随的唾液功能障碍是否可以通过免疫调节治疗来改善，而我们今年的结果为这一假设提供了支持。