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題名 | Lysophosphatidic Acid Up-regulates MT1-MMP Expression through a Gi-dependent Pathway in Human Umbilical Vein Endothelial Cells=Lysophosphatidic Acid經由Gi蛋白相關路徑在人類內皮細胞促使Membrane Type-1 Metalloproteinase之表現 |
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作者 | 林柏瑋; 黃元勵; 陳思原; 李心予; Lin, Po-wei; Huang, Yuan-li; Chen, Shee-uan; Lee, Hsinyu; |
期刊 | Taiwania |
出版日期 | 20091200 |
卷期 | 54:4 2009.12[民98.12] |
頁次 | 頁375-380 |
分類號 | 361.8 |
語文 | eng |
關鍵詞 | 人類臍帶靜脈內皮細胞; 細胞基質; LPA; MT1-MMP; MMP-2; HUVECs; ECM; |
中文摘要 | Lysophosphatidic acid (LPA) 是小分子量的水解磷酸脂。LPA 藉由接合到專一的G 蛋白受器影響許多細胞的功能,包括細胞增生、細胞遷移、細胞入侵和細胞分化。Matrix-metalloproteinases (MMPs) 是一群需要鋅離子才有活性的蛋白酶,MMPs 在細胞和細胞基質間 (Extracellular matrix, ECM) 的交互作用中扮演著重要的角色。再者,membrane type 1-metalloproteinase (MT1-MMP) 不只切除ECM 也會幫助metalloproteinase-2 (MMP-2, Gelatinase A) 的活化,MMP-2 已被證實在細胞遷移中扮演著重要的角色。我們之前的研究指出LPA 會促進MMP-2 在人類臍帶靜脈內皮細胞 (Human umbilical vein endothelial cells, HUVECs) 中的表現以及活性。在這份研究中,利用即時聚合酶放大技術 (real-time PCR) 以及西方點墨法 (Western blotting) ,我們進一步發現LPA 也會在HUVECs 中促使MT1-MMP 的訊息核醣核酸以及蛋白質表現增加。再者,藉由使用一些化學抑制物,我們發現LPA 促使MT1-MMP 的表現增加主要是經由Gi 路徑,且部分經由Gq。這結果提供了LPA 可能經由調節MT1-MMP 的表現來調控ECM 的新證據。 |
英文摘要 | Lysophosphatidic acid (LPA) is a low molecular weight lysophospholipid (LPL). Through binding to its specific G protein-coupled receptor family, LPA regulates various cellular functions, including proliferation, migration, invasion, and differentiation. Matrix-metalloproteinases (MMPs) are zinc-dependent protease and play important roles in regulating the interaction between cells and extracellular matrix (ECM). Among these MMPs, membrane type 1-metalloproteinase (MT1-MMP) not only degrades ECM protein but also activates metalloproteinase-2 (MMP-2, Gelatinase A), which are important to endothelial cell migration. Our previous study showed that LPA enhances MMP-2 expression and activity in human umbilical vein endothelial cells (HUVECs). In this study, we further revealed that LPA also induce MT1-MMP mRNA and protein expressions in HUVECs through real-time PCR and Western blotting, respectively. Furthermore, by applying chemical inhibitors, we found that LPA-induced MT1-MMP expression is mainly through a Gi- and partially through a Gq-dependent pathway. Our results provide new evidence that LPA might modulate ECM through regulating the expression of MT1-MMP. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。