研究幽門螺旋桿菌熱緊迫蛋白60的新功能---誘發TGF-Beta訊息傳遞之活性

Abstract

幽門螺旋桿菌於1980年代末期被發現以來，即成為胃腸科疾病及胃癌成因的重要研究課題。此菌已被證實可造成人類胃上皮細胞的破壞、癌變以及抑制宿主免疫系統等現象。在本實驗室先趨的研究中發現，幽門螺旋桿菌的熱迫性蛋白60（Hsp 60）會結合至TGF-β受體II啟動TGF-β的SMAD訊息傳遞路徑。因此在本實驗的第一階段中主要著重在生產高純度的Hsp60對胃上皮細胞進行刺激，並觀察其誘發TGF-β訊息狀況並利用cDNA array檢視Hsp60對胃上皮細胞基因表現的影響，此資料將著重在Hsp60對血管新生及轉移表現的影響。在第二階段中，本實驗室會測試幽門螺旋桿菌Hsp 60啟動TGF-β的SMAD訊息傳遞路徑對人類調控性T細胞（Treg）增生的影響，並觀察Hsp60對其功能性、轉錄因子的影響及其全面性基因表現的影響。根據文獻指出TGF-β對Treg功能十分重要，因此可預見Hsp60對Treg應有重要影響，故於本階段將可研究Hsp60對Treg功能的影響。

Helicobacter pylori (H. pylori, Hp) has become an important issue in the field of gastrointestinal disease and the development of gastric cancer since its discovery in late 1980’s. It has been confirmed that Hp can damage human gastric epithelial cells, cause oncogenesis and suppress host’s immunity. Our results indicated that H. pyori heat shock protein 60 (HpHsp60) could bind to TGF-β receptor II and trigger TGF-β regulated SMAD signal pathway. Thus, at the first stage of this project, we will purify high quality Hsp60 to treat gastric epithelial cells and observe how the HpHsp60 trigger the TGF-β signaling in the gastric epithelial cells and use the cDNA micro-array to survey the effect of Hsp60 on gastric epithelial cells. The information of cDNA micro-array will be focus on the effects to the angiogenesis and metastasis. At the second stage, we will measure the effect of HpHsp60-induced SMAD signal pathway on the proliferation for the human regulatory T cells (Treg) to observe how Hsp60 affects the physiological function, transcription factors, and the whole genomic expression of the purified Treg. Previous literatures revealed that TGF-β is important for the function of Treg, therefore Hsp60 should have important influence on Treg. At this stage, Hsp60 will be investigated its effects on the functions of Treg.