Thymosin β 4 stimulates directional migration of human umbilical vein endothelial cells

Abstract

Thymosin β 4 (Tβ 4 ) is a 4.9 kDa polypeptide that interacts with G‐actin and is thought to be an important mediator in cell proliferation, migration, and differentiation. Tβ 4 has been identified as a factor involved in the differentiation of human umbilical vein endothelial cells (HUVECs) cultured on Matrigel. Here we have used various in vitro and in vivo migration assays to demonstrate the role of Tβ 4 in endothelial cell migration. Our results demonstrate that Tβ 4 acts as a chemoattractant for endothelial cells, stimulating the migration of HUVECs in Boyden chambers four‐ to sixfold over that observed with media alone. Of the primary cell types tested, only human coronary artery cells responded to Tβ 4 treatment, suggesting that the migration activity of Tβ 4 was endothelial cell‐specific. Tβ 4 significantly accelerated the rate of migration into the scratch wounded area of a HUVEC monolayer. Tβ 4 treatment also increased the production of matrix metalloproteinases that may degrade the basement membrane during angiogenesis. Additional experiments using subcutaneously implanted Matrigel showed that Tβ 4 stimulated cell migration in vivo. These results provide the first direct evidence that Tβ 4 has chemoattractive activity and promotes angiogenesis by stimulating the migration of endothelial cells.—Malinda, K. M., Goldstein, A. L., Kleinman, H. K. Thymosin β 4 stimulates directional migration of human umbilical vein endothelial cells. FASEB J. 11, 474–481 (1997)