Ontogenetic transition in fetal wound transforming growth factor-beta regulation correlates with collagen organization.
Fetal rat skin transitions from scarless fetal-type repair to adult-type repair with scar between day 16 (E16) and day 18 (E18) of gestation (term = 21.5 days). Deficient transforming growth factor (TGF)-beta 1 and -beta 2 injury response has been proposed as a mechanism for scarless fetal-type repair. However, previous fetal studies have inconsistently reported the degree of TGF-beta induction after injury. To minimize developmental variables in fetal versus adult TGF-beta regulation, we narrowed our study to wounded fetal animals. We hypothesize that TGF-beta ligand and receptor expression will be differentially regulated during the transition from early gestation (E16) wounds manifesting scarless fetal-type repair to late gestation (E19) wounds manifesting adult-type repair with scar. In this study, decreased and rapidly cleared TGF-beta 1 and -beta 2 expression accompanied by increased and prolonged TGF-beta 3 levels in wounded E16 animals correlated with organized collagen deposition. In contrast, increased and prolonged TGF-beta 1 and -beta 2 expression accompanied by decreased and delayed TGF-beta 3 expression in wounded E19 animals correlated with disorganized collagen architecture. Similarly, expression of TGF-beta receptors type I and II were also increased or prolonged in E19 animals. Our results implicate increased TGF-beta 1, -beta 2, and decreased TGF-beta 3 expression, as well as increased type I and II receptor expression in late gestation fetal scar formation.
Soo
Chia
C
Department of Surgery, University of California, Los Angeles, California 90095, USA.
Beanes
Steven R
SR
Hu
Fei-Ya
FY
Zhang
Xinli
X
Dang
Catherine
C
Chang
Grace
G
Wang
Yubert
Y
Nishimura
Ichiro
I
Freymiller
Earl
E
Longaker
Michael T
MT
Lorenz
H Peter
HP
Ting
Kang
K
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D004801:Eosine Yellowish-(YS); D005260:Female; D006416:Hematoxylin; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D049188:Prenatal Injuries; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000196:embryology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing; D014950:Wounds, Penetrating / Q000473:pathology / Q000503:physiopathology
D020033:Protein Isoforms; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003094:Collagen; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin