The Healing Effects of TGF-β

Abstract

Proper wound healing requires orderly migration of multiple cell types. In humans, epidermal keratinocytes (HKs) move across the wound to form a new continuous epithelial layer. Dermal cells like dermal fibroblasts (DFs) and human dermal microvascular endothelial cells (HDMECs) move in to restore the extracellular matrix and help build new blood vessels. But how do these cells know when and where to do their work? New work from Bandyopadhyay et al. suggests that one important factor is that cells at the wound are first exposed to plasma (blood liquid without the cells), then serum (the cell-free liquid that remains after blood clotting), and then again to plasma. The authors observed the effects of serum and plasma on the various cell types in an assay in which cells left visible tracks on a surface of extracellular matrix coated with colloidal gold or in an in vitro wound-healing assay. Plasma stimulated migration of dermal cells (DFs and HDMECs) but had little effect on epidermal HKs. Conversely, serum stimulated migration of HKs but had little effect on DFs and HDMECs. The authors suspected transforming growth factor-β (TGF-β) as a factor that could account for these differential responses because it is relatively abundant in serum and scarce or undetectable in plasma. Cells responded to serum from which the TGF-β3 isoform had been removed with antibodies as though they were responding to plasma. The authors also found that type II TGF-β receptors were abundant in dermal cells but less prevalent in epidermal cells. Exogenous expression of TGF-βRII in HKs caused the cell to respond to serum with reduced, rather than enhanced, motility. When short inhibitory RNA was used to decrease expression of TGF-βRII in dermal cells, their migratory responses to plasma and serum were reversed. The authors propose that the sequential exposure of cells at a wound to plasma, then serum, and then plasma again coordinates the movement of the various cell types to allow tissue remodeling and healing. Wounds that fail to heal are a problem in certain disease states and in the elderly, and better understanding of the orchestration of the normal healing process may permit more effective use of growth-factor therapies to enhance healing of refractory wounds in the clinic. B. Bandyopadhyay, J. Fan, S. Guan, Y. Li, M. Chen, D. T. Woodley, W. Li, A "traffic control" role for TGFβ3: Orchestrating dermal and epidermal cell motility during wound healing. J. Cell Biol. 172 , 1093-1105 (2006). [Abstract] [Full Text]