Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair.
Fibroblast growth factors (FGFs) are a family of 21 cytokines with a broad spectrum of activities, including regulation of cell proliferation, differentiation, and migration. The various FGFs bind to one or more of four different tyrosine kinase receptor types. FGFs 1, 2, 5, 7, and 10 are up-regulated during adult cutaneous wound healing. However, the expression of FGFs during fetal skin development and scarless wound healing has not been characterized. It was hypothesized that differential expression of FGF isoforms and receptors occurs during fetal skin development and that this differential expression pattern may regulate the transition from scarless repair to healing with scar formation. Excisional wounds (2 mm) were created on fetal rats at gestational days 16.5 (scarless) (one wound per fetus, n = 36 fetuses) and 19.5 (scarring) (one wound per fetus, n = 36 fetuses). Wounds were harvested at 24, 48, and 72 hours. Survival until wound harvest ranged from 66 to 75 percent for the gestational day 16 fetuses, and from 83 to 92 percent for the gestational day 19 fetuses. Nonwounded fetal skin from littermates (n = 12 fetuses per wound harvest time point) was used as the control. Wounds/skins were pooled by harvest time point, and RNA was isolated from pooled wounds/skins. Reduced-cycle, specific-primer reverse transcriptase-polymerase chain reaction was performed to determine the expression of FGF isoforms 2, 5, 7, 9, and 10 and FGF receptors 1, 2, and 4 in wounds relative to unwounded skin.In unwounded fetal skin, FGF isoform 5 expression more than doubled at birth. FGF 10 expression doubled during the transition period. FGF 7 expression increased more than sevenfold at birth. Expression of FGF isoforms 2 and 9 did not change during late fetal skin development. The expression of FGF receptors 1, 2, and 4 increased at birth. After wounding, expression of FGF isoforms 7 and 10 was down-regulated in scarless wounds, whereas FGF receptor 2 expression decreased in both scarless and scar-forming wounds. Expression of FGF isoforms 5 and 9 did not change in scarless wounds. FGF receptor 2 expression was down-regulated in both scarless and scarring wounds, but at an earlier and more sustained level in scarless wounds. Receptor type 4 expression increased in scarring wounds, whereas type 1 expression did not change in either scarless or scarring wounds. These results demonstrate an overall down-regulation of FGF expression during scarless healing.
Dang
Catherine M
CM
Division of Plastic Surgery, Department of Surgery, School fo Medicine, University of California, Los Angeles, California, USA.
Beanes
Steven R
SR
Soo
Chia
C
Ting
Kang
K
Benhaim
Prosper
P
Hedrick
Marc H
MH
Lorenz
H Peter
HP
D000818:Animals; D002921:Cicatrix / Q000378:metabolism; D062109:Dermatologic Surgical Procedures; D005260:Female; D005333:Fetus / Q000601:surgery*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D005865:Gestational Age; D015603:Keratinocytes / Q000378:metabolism; D011247:Pregnancy; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000196:embryology / Q000378:metabolism*; D014945:Wound Healing
C496455:Fgf7 protein, rat; D020033:Protein Isoforms; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors