title: Rapid closure of midgestational excisional wounds in a fetal mouse model is associated with altered transforming growth factor-beta isoform and receptor expression.
abstract: BACKGROUND
  Many pediatric diseases are characterized by excessive tissue contraction. Because of a poor understanding of contraction, few therapies exist. We developed a murine fetal excisional wound model of contraction and theorize that wound closure is associated with changes in transforming growth factor-beta (TGF-beta) expression.
  
  
  METHODS
  Pregnant FVB mice underwent hysterotomy at midgestational (E15) or late-gestational (E18) ages. Three-millimeter excisional wounds were made in fetuses and harvested at 32 hours. Real-time polymerase chain reaction was performed for TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-1, and TbetaR-2 in wounds and normal skin and normalized to glyceraldehyde-3-phosphate dehydrogenase. Data were analyzed by paired t test (P < .05). H&E staining of wounds was performed.
  
  
  RESULTS
  E15 wounds (80.5% +/- 4.4%) were smaller than E18 wounds (10.4% +/- 10.5%; P < .001) at 32 hours. E15 wounds expressed higher levels of TGF-beta1 compared with normal skin (P = .001). TbetaR-2 levels were elevated in E15 and E18 wounds compared with their respective normal skin (P = .02, P = .01) and in E18 normal skin compared with E15 normal skin (P = .002).
  
  
  CONCLUSIONS
  This study demonstrates that rapid midgestational wound closure in a murine model is associated with increased TGF-beta1 and TbetaR-2 expression. Elucidating the role of the TGF-beta pathways may lead to an improved understanding of wound contraction.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Medical College of Virginia Hospitals, Virginia Commonwealth University Health System, P.O. Box 980015, Richmond, VA 23298-0015, USA.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Robert P
authors.initials: RP
authors.lastname: McKinstry
authors.forename: Virginia
authors.initials: V
authors.lastname: Sykes
authors.forename: David A
authors.initials: DA
authors.lastname: Lanning
mesh_terms: D030201:Activin Receptors, Type I / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D005865:Gestational Age; D020883:Hysterotomy; D051379:Mice; D023421:Models, Animal; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D020033:Protein Isoforms / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000196:embryology / Q000293:injuries* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis / Q000235:genetics; D053782:Transforming Growth Factor beta3 / Q000096:biosynthesis / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C509042:Tgfb2 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; 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