Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture.

TLDR

In a wounded BAE monolayer, endothelial cells spontaneously migrate into the denuded area. Pericytes or smooth muscle cells plated at low density into the wound inhibit endothelial cell migration in a cell‑number‑ and contact‑dependent manner, an effect mediated by activation of latent TGF‑β1‑like molecules via plasmin, as shown by reversal with anti‑TGF‑β1 antibodies, inhibition by plasmin inhibitors, and direct inhibition when exogenous TGF‑β1 is added.

Abstract

When a confluent monolayer of bovine aortic endothelial (BAE) cells is wounded with a razor blade, endothelial cells (ECs) spontaneously move into the denuded area. If bovine pericytes or smooth muscle cells (SMCs) are plated into the denuded area at low density, they block the movement of the ECs. This effect is dependent upon the number of cells plated into the wound area and contact between ECs and the plated cells. Antibodies to transforming growth factor-beta 1 (TGF-beta 1) abrogate the inhibition of BAE cell movement by pericytes or SMCs. TGF-beta 1, if added to wounded BAE cell monolayers, also inhibits cell movement. When cultured separately, BAE cells, pericytes, and SMCs each produce an inactive TGF-beta 1-like molecule which is activated in BAE cell-pericyte or BAE cell-SMC co-cultures. The activation appears to be mediated by plasmin as the inhibitory effect on cell movement in co-cultures of BAE cells and pericytes is blocked by the inclusion of inhibitors of plasmin in the culture medium.