Lysophosphatidic Acid Up-regulates MT1-MMP Expression Through a G(subscript i)-dependent Pathway in Human Umbilical Vein Endothelial Cells

Lysophosphatidic Acid經由G(下標 i)蛋白相關路徑在人類內皮細胞促使Membrane Type-1 Metalloproteinase之表現

林柏瑋(Po-Wei Lin) ； 黃元勵(Yuan-Li Huang) ； 黃元勵(Yuan-Li Huang) ； 陳思原(Shee-Uan Che) ； 李心予(Hsin-Yu Lee)

《TAIWANIA》 54卷4期 (2009/12) Pp. 375-380

https://doi.org/10.6165/tai.2009.54(4).375

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 type1-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G(下標 i)路徑，且部分經由G(下標 q)。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。

關鍵字

LPA ； MT1-MMP ； MMP-2 ； 人類臍帶靜脈內皮細胞 ； 細胞基質

並列摘要

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 G(subscript i)- and partially through a G(subscript q)-dependent pathway. Our results provide new evidence that LPA might modulate ECM through regulating the expression of MT1-MMP.

並列關鍵字

LPA ； MT1-MMP ； MMP-2 ； HUVECs ； ECM