MT1-MMP and Egr-1 Expressions Induced by Different Strengths of Shear Stress in Endothelial Cell

ABSTRACT

PURPOSE: Membrane type-1-matrix metalloproteinase (MT1-MMP) plays a key role in endothelial cell (EC) migration, matrix remodeling, and angiogenesis. Previous studies demonstrated that a cyclic strain (CS) increases MT1-MMP expression by displacing specific protein 1(Sp1) with increased early growth response-1 (Egr-1) expression; and shear stress (SS) decreases MT1-MMP expression by Sp1 phosphorylation. However, the difference in MT1-MMP expression according to the change of SS is poorly understood. The aim of this study is to determine the effects of low or high SS on Egr-1 and MT1-MMP transcription and translation. METHOD: Bovine aortic ECs were exposed to oscillatory SS (low=0.1 dyne/cm2 or high=14 dyne/cm2) with orbital shaker for 0, 1, 4, or 8 hours. Activation of Egr-1 and MT1-MMP was assessed by the Northern blot and Western blot. RESULT: Although Egr-1 mRNA transcription and protein translation were induced (7.3-, 5.8-fold and 4.0-, 4.9-fold, respectively) in response to low SS (n=5, 0, 1, and 4 hr; P<0.05), MT1-MMP mRNA transcription and protein levels did not change remarkably. Egr-1 mRNA transcription and translation were induced (7.6-fold at 1 hr; 3.7- and 5.2-fold at 1 and 4 hr, respectively) in response to high SS (n=5; P<0.05). We observed that high SS decreased MT1-MMP mRNA transcription and translation in a time-dependent fashion (10%, 50%, and 90% reduction at 1, 4, and 8 hr, respectively; n=5, P<0.05). CONCLUSION: High SS induces Egr-1 up-regulation and inhibits MT1-MMP expression. But low SS has no effect on MT1-MMP expression in spite of Egr-1 up-regulation. These observations illustrate that the expression of MT1-MMP is dependent on, not only the type of hemodynamic forces, but also the strength of force (SS) in vascular endothelial cells.