151 A “Traffic Control” Role for TGF-Beta in Skin Cell Motility During Wound Healing

Abstract

Skin wound healing requires temporally and spatially coordinated motility of multiple skin cell types. The limited success of current skin wound care is due to lack of understanding about how the healing processes begin, progress, and complete. One of the most dramatic environmental changes in an acute wound is the transition from plasma to serum. The cells in the wound come into contact with serum, instead of a filtrate of plasma, for the first time. We report here that this transition differentially regulates the migration of various skin cell types. Plasma promotes dermal fibroblast and endothelia cell, but not keratinocyte and melanocyte, motility. In contrast, serum selectively promotes keratinocyte motility and inhibits fibroblast and endothelial cell motility. The key regulators are the increased transforming growth factor-beta (TGF-beta) in serum and the distinct TGF-beta receptor (I, II and III) profiles in different cell types. TGF-beta selectively inhibits fibroblast and endothelial cell, but not keratinocyte and melanocyte, migration. Neutralization of TGF-beta function in serum eliminates the differential effects between serum and plasma. Manipulations of the TGF-beta receptor profiles in the cells, especially TGF-beta receptor II and III, convert TGF-beta-insensitive cell types to sensitive cell types and vice versa, and their responses to plasma and serum. This is the first study that reveals a molecular mechanism for coordinating multiple skin cell-type motility in wounds.