Transforming growth factor-β3 affects plasminogen activator inhibitor-1 expression in fetal mice and modulates fibroblast-mediated collagen gel contraction

Wai Yee Li, Eunice Huang, Marek Dudas, Vesa Kaartinen, David Warburton, Tai Lan Tuan

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

For over two decades, the precise role of transforming growth factor-β (TGF-β) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF-β3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF-β downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF-β3 and PAI-1 was investigated using embryonic day 14.5 TGF-β3 knockout (ko) mice. The results showed increased PAI-1 expression in the epidermis and dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased PAI-1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF-β3 knockout fibroblasts were placed into three-dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell-matrix interaction. These findings provide a further avenue for the interactive role of TGF-β3 and PAI-1 during fetal scarless repair.

Original languageEnglish (US)
Pages (from-to)516-525
Number of pages10
JournalWound Repair and Regeneration
Volume14
Issue number5
DOIs
StatePublished - Sep 1 2006

Fingerprint

Plasminogen Activator Inhibitor 1
Transforming Growth Factors
Collagen
Fibroblasts
Gels
Knockout Mice
Skin
Dermis
Conditioned Culture Medium
Fetal Development
Epidermis
Cell Communication
Protein Isoforms
Fibrosis
Embryonic Structures
Extremities
Phenotype
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Surgery
  • Dermatology

Cite this

Transforming growth factor-β3 affects plasminogen activator inhibitor-1 expression in fetal mice and modulates fibroblast-mediated collagen gel contraction. / Li, Wai Yee; Huang, Eunice; Dudas, Marek; Kaartinen, Vesa; Warburton, David; Tuan, Tai Lan.

In: Wound Repair and Regeneration, Vol. 14, No. 5, 01.09.2006, p. 516-525.

Research output: Contribution to journalArticle

@article{898c518548bd4684830873c33e593b6e,
title = "Transforming growth factor-β3 affects plasminogen activator inhibitor-1 expression in fetal mice and modulates fibroblast-mediated collagen gel contraction",
abstract = "For over two decades, the precise role of transforming growth factor-β (TGF-β) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF-β3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF-β downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF-β3 and PAI-1 was investigated using embryonic day 14.5 TGF-β3 knockout (ko) mice. The results showed increased PAI-1 expression in the epidermis and dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased PAI-1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF-β3 knockout fibroblasts were placed into three-dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell-matrix interaction. These findings provide a further avenue for the interactive role of TGF-β3 and PAI-1 during fetal scarless repair.",
author = "Li, {Wai Yee} and Eunice Huang and Marek Dudas and Vesa Kaartinen and David Warburton and Tuan, {Tai Lan}",
year = "2006",
month = "9",
day = "1",
doi = "10.1111/j.1743-6109.2006.00158.x",
language = "English (US)",
volume = "14",
pages = "516--525",
journal = "Wound Repair and Regeneration",
issn = "1067-1927",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Transforming growth factor-β3 affects plasminogen activator inhibitor-1 expression in fetal mice and modulates fibroblast-mediated collagen gel contraction

AU - Li, Wai Yee

AU - Huang, Eunice

AU - Dudas, Marek

AU - Kaartinen, Vesa

AU - Warburton, David

AU - Tuan, Tai Lan

PY - 2006/9/1

Y1 - 2006/9/1

N2 - For over two decades, the precise role of transforming growth factor-β (TGF-β) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF-β3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF-β downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF-β3 and PAI-1 was investigated using embryonic day 14.5 TGF-β3 knockout (ko) mice. The results showed increased PAI-1 expression in the epidermis and dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased PAI-1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF-β3 knockout fibroblasts were placed into three-dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell-matrix interaction. These findings provide a further avenue for the interactive role of TGF-β3 and PAI-1 during fetal scarless repair.

AB - For over two decades, the precise role of transforming growth factor-β (TGF-β) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF-β3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF-β downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF-β3 and PAI-1 was investigated using embryonic day 14.5 TGF-β3 knockout (ko) mice. The results showed increased PAI-1 expression in the epidermis and dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased PAI-1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF-β3 knockout fibroblasts were placed into three-dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell-matrix interaction. These findings provide a further avenue for the interactive role of TGF-β3 and PAI-1 during fetal scarless repair.

UR - http://www.scopus.com/inward/record.url?scp=33749147653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749147653&partnerID=8YFLogxK

U2 - 10.1111/j.1743-6109.2006.00158.x

DO - 10.1111/j.1743-6109.2006.00158.x

M3 - Article

VL - 14

SP - 516

EP - 525

JO - Wound Repair and Regeneration

JF - Wound Repair and Regeneration

SN - 1067-1927

IS - 5

ER -