Exogenous transforming growth factor β2 modulates collagen I and collagen III synthesis in proliferative scar xenografts in nude rats

Xue Wang, Paul Smith, Lee Li-Qun Pu, Y. J. Kim, Francis Ko, Martin C. Robson

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Background. Keloid and hypertrophic scars are fibrous dermal tumors characterized by overabundant collagen deposition. Previous studies demonstrated that exogenous transforming growth factor β (TGF-β) might increase collagen production in incisional wound models and in vitro. Using an in vivo model of human scar xenografts maintained in congenitally athymic, asplenic 'nude' rats, we examined endogenous TGF-β2, collagen I, and collagen III levels in keloids and burn hypertrophic scars treated with TGF- β2 and TGF-β2 antibody. Methods. Fresh keloid and burn hypertrophic scar specimens excised from human subjects were explanted to pedicled flaps based on the superficial inferior epigastric vessels in athymic 'nude' rats. These flaps were allowed to mature for 3 weeks, after which the scar explants were directly perfused with 200 ng of TGF-β2 or 250 μg of TGF-β2 antibody daily for 5 consecutive days, then again on Days 10, 15, and 20. Biopsies were taken 30 and 120 days following the initiation of treatment. Immunohistochemical staining was then performed for TGF-β2, collagen I, and collagen III. The intensity of staining was quantified. Results. Our results demonstrated that treatment of human proliferative scars with exogenous TGF- β2 results in a significant increase in endogenous TGF-β2, collagen I, and collagen III production. By contrast, exogenous addition of anti-TGF-β2 antibody significantly decreased endogenous TGF-β2, collagen I, and collagen III production. Conclusion. This study supports a causative role for TGF-β2 in the formation of proliferative scars and suggests that TGF-β2 antibody may be a new potential antiscarring agent.

Original languageEnglish (US)
Pages (from-to)194-200
Number of pages7
JournalJournal of Surgical Research
Volume87
Issue number2
DOIs
StatePublished - Dec 1999
Externally publishedYes

Fingerprint

Nude Rats
Transforming Growth Factors
Heterografts
Cicatrix
Collagen
Hypertrophic Cicatrix
Keloid
Antibodies
Staining and Labeling
Surgical Flaps

Keywords

  • Burn hypertrophic scar
  • Keloid scar
  • Nude rat
  • Transforming growth factor β
  • Transforming growth factor β antibody

ASJC Scopus subject areas

  • Surgery

Cite this

Exogenous transforming growth factor β2 modulates collagen I and collagen III synthesis in proliferative scar xenografts in nude rats. / Wang, Xue; Smith, Paul; Pu, Lee Li-Qun; Kim, Y. J.; Ko, Francis; Robson, Martin C.

In: Journal of Surgical Research, Vol. 87, No. 2, 12.1999, p. 194-200.

Research output: Contribution to journalArticle

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abstract = "Background. Keloid and hypertrophic scars are fibrous dermal tumors characterized by overabundant collagen deposition. Previous studies demonstrated that exogenous transforming growth factor β (TGF-β) might increase collagen production in incisional wound models and in vitro. Using an in vivo model of human scar xenografts maintained in congenitally athymic, asplenic 'nude' rats, we examined endogenous TGF-β2, collagen I, and collagen III levels in keloids and burn hypertrophic scars treated with TGF- β2 and TGF-β2 antibody. Methods. Fresh keloid and burn hypertrophic scar specimens excised from human subjects were explanted to pedicled flaps based on the superficial inferior epigastric vessels in athymic 'nude' rats. These flaps were allowed to mature for 3 weeks, after which the scar explants were directly perfused with 200 ng of TGF-β2 or 250 μg of TGF-β2 antibody daily for 5 consecutive days, then again on Days 10, 15, and 20. Biopsies were taken 30 and 120 days following the initiation of treatment. Immunohistochemical staining was then performed for TGF-β2, collagen I, and collagen III. The intensity of staining was quantified. Results. Our results demonstrated that treatment of human proliferative scars with exogenous TGF- β2 results in a significant increase in endogenous TGF-β2, collagen I, and collagen III production. By contrast, exogenous addition of anti-TGF-β2 antibody significantly decreased endogenous TGF-β2, collagen I, and collagen III production. Conclusion. This study supports a causative role for TGF-β2 in the formation of proliferative scars and suggests that TGF-β2 antibody may be a new potential antiscarring agent.",
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AB - Background. Keloid and hypertrophic scars are fibrous dermal tumors characterized by overabundant collagen deposition. Previous studies demonstrated that exogenous transforming growth factor β (TGF-β) might increase collagen production in incisional wound models and in vitro. Using an in vivo model of human scar xenografts maintained in congenitally athymic, asplenic 'nude' rats, we examined endogenous TGF-β2, collagen I, and collagen III levels in keloids and burn hypertrophic scars treated with TGF- β2 and TGF-β2 antibody. Methods. Fresh keloid and burn hypertrophic scar specimens excised from human subjects were explanted to pedicled flaps based on the superficial inferior epigastric vessels in athymic 'nude' rats. These flaps were allowed to mature for 3 weeks, after which the scar explants were directly perfused with 200 ng of TGF-β2 or 250 μg of TGF-β2 antibody daily for 5 consecutive days, then again on Days 10, 15, and 20. Biopsies were taken 30 and 120 days following the initiation of treatment. Immunohistochemical staining was then performed for TGF-β2, collagen I, and collagen III. The intensity of staining was quantified. Results. Our results demonstrated that treatment of human proliferative scars with exogenous TGF- β2 results in a significant increase in endogenous TGF-β2, collagen I, and collagen III production. By contrast, exogenous addition of anti-TGF-β2 antibody significantly decreased endogenous TGF-β2, collagen I, and collagen III production. Conclusion. This study supports a causative role for TGF-β2 in the formation of proliferative scars and suggests that TGF-β2 antibody may be a new potential antiscarring agent.

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