中文摘要
寻找粘膜修复三叶因子受体，探索其分子机制是国际上致力解决的问题。betagamm-晶状体蛋白在眼睛晶状体以外功能和分子作用机制未知。本项目以两栖动物肽类毒素为主要研究对象，首次阐明了细胞膜G-蛋白偶联受体PAR1是两栖动物粘膜修复三叶因子Bm-TFF2作用的膜受体；以此为线索，揭示人三叶因子2通过作用于PAR4而诱导细胞迁移的分子生物学机制。发现抑素蛋白prohibitins(PHB1和PHB2)调节PAR1受体激活和信号转导的功能。在两栖动物中，发现betagamma-晶状体蛋白和三叶因子天然复合物betagamma-CAT的存在，并揭示通过结合－胞内转运－转录调节的方式，该betagamma-晶状体蛋白与三叶因子协同作用通过一条全新的细胞信号调节通路而调节细胞迁移和凋亡。项目深入揭示了两栖动物肽类毒素分子与功能多样性及环境适应机制。获得包括抗菌肽、抗氧化肽、免疫活性肽等在内的700余条生物活性肽分子，为生物医学应用打下基础。目前已经以通信作者发表SCI论文18篇，获授权发明专利2项，申请发明专利3项，获云南省科学技术奖一等奖一项。已培养毕业博士8人。主要研究结果正整理论文发表。
英文摘要
For a long time, trefoil factors are orphan ligands. The membrane receptors and their molecular action mechanisms are open questions for scientists in the field. Non-lens betagamma-crystallins are widely expressed in epithelial systems outside of eye lens, but their functions and molecular mechanisms are unknown. Based on the studies on proteins and peptides from amphibians, the results obtained in this project show that the activation of protease-activated receptor (PAR) 1 by a frog trefoil factor Bm-TFF2, and the activation of PAR4 by human TFF2. In addition, It was revealed that prohibitins are expressed in platelet membranes, and are involved in the regulation of PAR1 signaling, making them as novel attractive drug targets. A natural complex of non-lens betagamma-crystallin and trefoil factor, named betagamma-CAT, was identified from frog Bombina maxima skin. The protein is highly toxic to mammals, causing endothelium-dependent heart failure. betagamma-CAT was able to induce cell migration and cell apoptosis at pM and nM concentrations, respectively. It was rapidly endocytosed and acts intracellularly. The gene expression profiles induced by betagamma-CAT treatment is in accordance with that observed in wound healing, suggesting the complex plays a important role in skin wound healing and immunity. About 700
结题摘要
寻找粘膜修复三叶因子受体，探索其分子机制是国际上致力解决的问题。betagamm-晶状体蛋白在眼睛晶状体以外功能和分子作用机制未知。本项目以两栖动物肽类毒素为主要研究对象，首次阐明了细胞膜G-蛋白偶联受体PAR1是两栖动物粘膜修复三叶因子Bm-TFF2作用的膜受体；以此为线索，揭示人三叶因子2通过作用于PAR4而诱导细胞迁移的分子生物学机制。发现抑素蛋白prohibitins(PHB1和PHB2)调节PAR1受体激活和信号转导的功能。在两栖动物中，发现betagamma-晶状体蛋白和三叶因子天然复合物betagamma-CAT的存在，并揭示通过结合－胞内转运－转录调节的方式，该betagamma-晶状体蛋白与三叶因子协同作用通过一条全新的细胞信号调节通路而调节细胞迁移和凋亡。项目深入揭示了两栖动物肽类毒素分子与功能多样性及环境适应机制。获得包括抗菌肽、抗氧化肽、免疫活性肽等在内的700余条生物活性肽分子，为生物医学应用打下基础。目前已经以通信作者发表SCI论文18篇，获授权发明专利2项，申请发明专利3项，获云南省科学技术奖一等奖一项。已培养毕业博士8人。主要研究结果正整理论文发表。