A "traffic control" role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing.
Cell migration is a rate-limiting event in skin wound healing. In unwounded skin, cells are nourished by plasma. When skin is wounded, resident cells encounter serum for the first time. As the wound heals, the cells experience a transition of serum back to plasma. In this study, we report that human serum selectively promotes epidermal cell migration and halts dermal cell migration. In contrast, human plasma promotes dermal but not epidermal cell migration. The on-and-off switch is operated by transforming growth factor (TGF) beta3 levels, which are undetectable in plasma and high in serum, and by TGFbeta receptor (TbetaR) type II levels, which are low in epidermal cells and high in dermal cells. Depletion of TGFbeta3 from serum converts serum to a plasmalike reagent. The addition of TGFbeta3 to plasma converts it to a serumlike reagent. Down-regulation of TbetaRII in dermal cells or up-regulation of TbetaRII in epidermal cells reverses their migratory responses to serum and plasma, respectively. Therefore, the naturally occurring plasma-->serum-->plasma transition during wound healing orchestrates the orderly migration of dermal and epidermal cells.
Department of Dermatology and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Balaji
B
Bandyopadhyay
Jianhua
J
Fan
Shengxi
S
Guan
Yong
Y
Li
Mei
M
Chen
David T
DT
Woodley
Wei
W
Li
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D020405:Dermis / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D010949:Plasma / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D044967:Serum / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D053782:Transforming Growth Factor beta3; D014945:Wound Healing
D000906:Antibodies; D016895:Culture Media, Serum-Free; D011509:Proteoglycans; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; C071736:betaglycan; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II