1. Connective Tissue Growth Factor (CTGF/CCN2) Mediates Angiogenic Effect of S1P in Human Dermal Microvascular Endothelial Cells.
- Author
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MARKIEWICZ, MARGARET, NAKERAKANTI, SASHIDHAR S., KAPANADZE, BAGRAT, GHATNEKAR, ANGELA, and TROJANOWSKA, MARIA
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CONNECTIVE tissue development , *NEOVASCULARIZATION , *VASCULAR endothelium , *CELL migration , *COLLAGEN , *SMALL interfering RNA , *WOUND healing - Abstract
Please cite this paper as: Markiewicz, Nakerakanti, Kapanadze, Ghatnekar and Trojanowska (2011). Connective Tissue Growth Factor (CTGF/CCN2) Mediates Angiogenic Effect of S1P in Human Dermal Microvascular Endothelial Cells. Microcirculation 18(1), 1-11. Abstract Objective: The primary objective of this study was to examine the potential interaction between S1P, a pleiotropic lipid mediator, and CTGF/CCN2, a secreted multimodular protein, in the process of endothelial cell migration. The secondary objective was to determine whether C- and N-terminal domains of CTGF/CCN2 have a specific function in cell migration. Materials and Methods: Migration of HDMECs was examined in monolayer wound healing 'scratch' assay, whereas capillary-like tube formation was examined in three-dimensional collagen co-culture assays. Results: We observed that S1P stimulates migration of HDMECs concomitant with upregulation of CTGF/CCN2 expression. Furthermore, the blockade of endogenous CTGF/CCN2 via siRNA abrogated S1P-induced HDMEC migration and capillary-like tube formation. Full-length CTGF induced cell migration and capillary-like tube formation with a potency similar to that of S1P, while C-terminal domain of CTGF was slightly less effective. However, N-terminal domain had only a residual activity in inducing capillary-like tube formation. Conclusions: This study revealed that CTGF/CCN2 is required for the S1P-induced endothelial cell migration, which suggests that CTGF/CCN2 may be an important mediator of S1P-induced physiological and pathological angiogenesis. Moreover, this study shows that the pro-migratory activity of CTGF/CCN2 is located in the C-terminal domain. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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