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).

CONCLUSION:

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: Stephanie R Goldberg, Robert P McKinstry, Virginia Sykes, David A Lanning
• Journal: Journal of pediatric surgery (J Pediatr Surg) Vol. 42 Issue 6 Pg. 966-71; discussion 971-3 (Jun 2007) ISSN: 1531-5037 [Electronic] United States
• PMID: 17560204 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Isoforms
• RNA, Messenger
• Receptors, Transforming Growth Factor beta
• Tgfb2 protein, mouse
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Transforming Growth Factor beta2
• Transforming Growth Factor beta3
• Protein Serine-Threonine Kinases
• Activin Receptors, Type I
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Activin Receptors, Type I (biosynthesis, genetics)
• Animals
• Female
• Gene Expression Regulation
• Gestational Age
• Hysterotomy
• Mice
• Models, Animal
• Polymerase Chain Reaction
• Pregnancy
• Protein Isoforms (physiology)
• Protein Serine-Threonine Kinases
• RNA, Messenger (biosynthesis, genetics)
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (biosynthesis, genetics, physiology)
• Skin (embryology, injuries, metabolism)
• Transforming Growth Factor beta (physiology)
• Transforming Growth Factor beta1 (biosynthesis, genetics)
• Transforming Growth Factor beta2 (biosynthesis, genetics)
• Transforming Growth Factor beta3 (biosynthesis, genetics)
• Wound Healing (physiology)