High levels of TβRII (green) on dermal cells (top), but not epidermal cells (bottom), bind serum TGFβ3 and prevent dermal cell migration.

Skin cell types enter wounds at different times to first seal and then heal. This ordering is directed by the antimigration effect of TGFβ3, according to Bandyopadhyay et al., on page 1093.

The first cells to enter an injured site are epidermal keratinocytes, which migrate across to resurface and close the wound. Later come the deeper dermal cells, including fibroblasts and endothelial cells. Keratinocytes must migrate ahead of dermal cells, or the more aggressive fibroblasts will push them aside, causing scarring or even preventing healing.

The new results show that dermal cells, but not keratinocytes, are temporarily held at bay by the action of a serum-derived factor called TGFβ3. Intact skin is nourished by plasma. But when skin is wounded, plasma converts to serum—a complex mixture of plasma proteins plus newly released cytokines and proteinases.

Unlike plasma, serum is known to contain TGFβ. The TGFβ3 isoform, the group found, halted dermal cell migration. This response depended on high levels of the TβRII receptor on dermal cells. Keratinocytes, on the other hand, had low levels of TβRII and thus were able to migrate in the serum environment.

During healing, serum is replaced by plasma, which the group's study suggested stimulated dermal cell migration to repair and remodel the wound interior. Chronic problems with wound healing might stem from a disorderly entry of fibroblasts or from the sluggish migration of keratinocytes or dermal cells.