Lysophosphatidic Acid Up-regulates MT1-MMP Expression through a Gi –dependent Pathway in Human Umbilical Vein Endothelial Cells

• Main Authors: Po-Wei Lin, Yuan-Li Huang, Shee-Uan Chen, Hsinyu Lee
• Format: Article
• Language: English
• Published: National Taiwan University 2009-11-01
• Series: Taiwania
• Subjects: LPA; MT1-MMP; MMP-2; HUVECs; ECM
• Online Access: http://tai2.ntu.edu.tw/taiwania/abstract.php?type=abstract&id=935

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.