Akt參與調控埃及斑蚊基質金屬蛋白酶之功能性研究

Abstract

蚊子為傳播瘧疾、登革熱以及西尼羅病毒等等疾病之元兇。由於目前缺乏有效疫苗防禦這些疾病，更嚴重的是蚊子對殺蟲劑以及病原對藥物已經出現抗藥性，造成全世界每年至少2百萬人死於這些由蚊子所傳播的疾病。因此我們極需開發對抗病媒蚊傳播疾病之新策略。MMP是一群基質金屬蛋白酶，先前研究指出不同物種的MMP具有不同功能。已知甲蟲MMP1與氣管發育、蛹變態以及先天性免疫有關。而果蠅MMP1在氣管生長以及胚胎發育扮演重要角色。我們實驗室先前研究發現埃及斑蚊之基質金屬蛋白酶1 (AaMMP1)參與蚊子卵黃發育之調控。因此我們想更進一步研究AaMMP1調控卵黃發育之機制以及其與TOR訊息傳遞之交互作用。我們以RNA干擾方式抑制埃及斑蚊TOR表現，結果顯示AaMMP1的蛋白質表現下降。因此我們想更進一步了解TOR之上游調控分子AKT對AaMMP1之影響。我們再以RNA干擾方式抑制埃及斑蚊AKT之基因表現，當AKT基因表現量下降也同時抑制AaMMP1的蛋白質表現。因此，本研究想探討埃及斑蚊MMP1的訊息傳遞調控機制，以提供演化高度保留性之MMP新觀點。此研究成果可提供未來制定有效控制蚊子傳播疾病的新策略。 關鍵詞: 埃及斑蚊、MMP1、TOR、AKT、卵黃生成

Mosquitoes are responsible for several infectious diseases such as malaria, dengue fever, West Nile fever…etc. Due to the unavailability of effective vaccines and the development of drug and insecticide resistance, more than 2 million people are killed by mosquito-borne diseases annually. Therefore, any possible avenue for developing novel control strategies against mosquito-borne diseases is urgently needed. MMP is a group of matrix metalloproteinase proteins. Previous study reports that MMP have many functional roles. It was shown that Tribolium MMP1 is related to tracheal development, pupal morphogenesis and innate immune responses. In Drosophila, MMP1 was demonstrated to play an important role in tracheal elongation, blastema formation. Our previous results revealed that Aedes aegypti MMP1 (AaMMP1) was involved in the regulation of vitellogenesis. Therefore, we will investigate the regulation mechanism of AaMMP1 and its interaction with TOR signaling pathway. The expression of AaMMP1 was inhibited with the RNAi-mediated silence of Aedes aegypti TOR. We also examine the effect of AKT, an upstream component of TOR signaling pathway, in the regulation of AaMMP1. Interestingly, silence of Aedes aegypti AKT strongly inhibited the expression of AaMMP1. Detail characterization of the regulation machinery of AaMMP1 will provide new insights into the evolutionaily conserved features of MMP. Information gathered in this study will pave the way toward the establishment of efficient strategies for vector control. Keywords: Aedes aegypti、MMP1、TOR、AKT、Vitellogenesis