Increased plasminogen activator inhibitor-1 in keloid fibroblasts may account for their elevated collagen accumulation in fibrin gel cultures

Tai Lan Tuan, Huayang Wu, Eunice Huang, Sheree S.N. Chong, Walter Laug, Diana Messadi, Paul Kelly, Anh Le

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Proteolytic degradation of the provisional fibrin matrix and subsequent substitution by fibroblast-produced collagen are essential features of injury repair. Immunohistochemical studies revealed that although dermal fibroblasts of normal scars and keloids expressed both urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1), keloid fibroblasts had a much higher PAI-1 expression. In long-term three-dimensional fibrin gel cultures (the in vitro fibroplasia model), normal fibroblasts expressed moderate and modulated activity levels of uPA and PAI-1. In contrast, keloid fibroblasts expressed a persistently high level of PAI-1 and a low level of uPA. The high PAI-1 activity of keloid fibroblasts correlated with their elevated collagen accumulation in fibrin gel cultures. Substituting collagen for fibrin in the gel matrix resulted in increased uPA activity and reduced collagen accumulation of keloid fibroblasts. Furthermore, decreasing PAI-1 activity of keloid fibroblasts in fibrin gel cultures with anti-PAI-1-neutralizing antibodies also resulted in a reduction in collagen accumulation by keloid fibroblasts. Cumulatively, these results suggest that PAI-1 overexpression is a consistent feature of keloid fibroblasts both in vitro and in vivo, and PAI-1 may play a causative role in elevated collagen accumulation of keloid fibroblasts.

Original languageEnglish (US)
Pages (from-to)1579-1589
Number of pages11
JournalAmerican Journal of Pathology
Volume162
Issue number5
DOIs
StatePublished - May 1 2003

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Keloid
Plasminogen Activator Inhibitor 1
Fibrin
Collagen
Fibroblasts
Gels
Urokinase-Type Plasminogen Activator
Neutralizing Antibodies
Cicatrix

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Increased plasminogen activator inhibitor-1 in keloid fibroblasts may account for their elevated collagen accumulation in fibrin gel cultures. / Tuan, Tai Lan; Wu, Huayang; Huang, Eunice; Chong, Sheree S.N.; Laug, Walter; Messadi, Diana; Kelly, Paul; Le, Anh.

In: American Journal of Pathology, Vol. 162, No. 5, 01.05.2003, p. 1579-1589.

Research output: Contribution to journalArticle

Tuan, Tai Lan ; Wu, Huayang ; Huang, Eunice ; Chong, Sheree S.N. ; Laug, Walter ; Messadi, Diana ; Kelly, Paul ; Le, Anh. / Increased plasminogen activator inhibitor-1 in keloid fibroblasts may account for their elevated collagen accumulation in fibrin gel cultures. In: American Journal of Pathology. 2003 ; Vol. 162, No. 5. pp. 1579-1589.
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AU - Kelly, Paul

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