Frangulin B抑制肺部纖維母細胞結締組織生長因子表現之機轉探討

Inhibitory Mechanisms of Frangulin B on Connective Tissue Growth Factor Expression in Human Lung Fibroblasts

李延宏(Yen-Hung Lee)

指導教授 ： 林建煌

臺北醫學大學/醫學院/醫學科學研究所/碩士(2010年)

https://doi.org/10.6831/TMU.2010.00214

摘要

本論文主要探討台灣鼠李Rhamnus formosana Matsum的中草藥中的主要成分Frangulin B抑制人類肺部纖維母細胞(WI-38) 受thrombin、endothelin-1 (ET-1)和bradykinin (BK) 引發之connective tissue growth factor (CTGF)表現之機制研究。細胞前處理Frangulin B (1-10 ?嵱) 再給予thrombin、endothelin-1 (ET-1)或bradykinin (BK)刺激，發現Frangulin B會以濃度相關方式分別抑制thrombin、ET-1和BK 所引發CTGF表現。進一步實驗證實Frangulin B沒有細胞毒性，Frangulin B (1-100 ?嵱)不會影響細胞存活率。Frangulin B (1-10 ?嵱)以濃度相關方式抑制thrombin和ET-1所誘導的signal transducer and activator of transcription 3 (STAT-3)和Janus kinase 2 (JAK-2)的磷酸化反應。然而，Frangulin B (1-10 ?嵱)卻無法抑制thrombin誘導Mitogen-activated protein kinases (MAPKs)的磷酸化反應。此外，Frangulin B (1-10 ?嵱)也以濃度相關方式抑制thrombin誘導collagen I 和alpha smooth muscle actin (??-SMA)的表現。綜合以上實驗結果顯示，Frangulin B可抑制thrombin誘導的纖維化物質產生，且經由抑制JAK-2蛋白激酶的活性而來。這些結果顯示，Frangulian B 是一個新的JAK-2的抑制劑可以發展成一種有效抑制肺部纖維化的藥物。

關鍵字

臺灣鼠李 ； 結締組織生長因子

並列摘要

In this project, we undertook to explore the action mechanism of Frangulin B, a main extract of Rhamnus formosana Matsumb, suppresses thrombin, endothelin-1 (ET-1) or bradykinin (BK)-induced connective tissue growth factor (CTGF) expression in human lung fibroblasts (WI-38). Pretreatment of cells with Frangulin B (1-10 ?嵱) attenuated thrombin, ET-1 and BK-induced CTGF expression in a concentration dependent manner. Cell were treated various concentrations of Frangulin B (1-100?嵱) , Frangulin B has no effect on WI-38 cell viability. Moreover, Frangulin B (1-10 ?嵱) inhibited signal transducer and activator of transcription 3 (STAT-3) and janus kinase 2 (JAK-2) phosphorylation in a concentration-dependent manner. However, Frangulin B (1-10 ?嵱) could not inhibit mitogen-activated protein kinases (MAPKs) including extracellular regulated protein kinase (ERK) and c-Jun-N-terminal kinase (JNK) phosphorylation. Using in vitro JAK-2 kinase assay, we found that Frangulin B directly inhibitied the JAK-2 kinase activity. In addition, Frangulin B inhibited thrombin-induced collagen I and ??-SMA expression. Taken together, we demonstrate Frangulin B inhibited thrombin-induced profibrosis protein in WI-38 cells; this inhibition is mediated by suppressing JAK-2 enzyme activity. Our results suggest that Frangulin B is a novel JAK-2 inhibitor and may be an effective anti-fibrosis drug.

並列關鍵字

Frangulin B ； CTGF

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