Expression of mRNA for Transforming Growth Factor-β1 Is Reduced in Hypertrophic Scar and Normal Dermal Fibroblasts Following Serial Passage In Vitro

1. Fibroblast cultures were established from biopsies of hypertrophic scar and normal dermis taken from nine patients recovering from second- and third-degree burns. The capacity of these fibroblasts to synthesize the small proteoglycan decorin was assessed by quantitative Western blot analysis of conditioned medium collected from confluent cultures. Levels of mRNA for decorin were assessed by quantitative Northern analysis. Since transforming growth factor-β1 is implicated in various fibrotic conditions, including post-burn hypertrophic scar, its effect on decorin synthesis by these paired fibroblast cell strains was assessed. 2. Production of decorin was lower in all cell strains of hypertrophic scar fibroblasts tested, compared with normal dermal fibroblasts cultured from the same patients (mean 49 ± 23%; P < 0.001, n = 9). Levels of mRNA for decorin were also lower (mean 59 ± 28%; P < 0.02, n = 7) but those for biglycan and versican were not significantly different. Four pairs of cell strains were examined at more than one passage and the differences in decorin protein were found to be phenotypically persistent. Treatment of confluent cultures with transforming growth factor-β1 for 3 days caused a reduction in both decorin protein and mRNA in all six strains of hypertrophic scar fibroblasts tested and in five of six strains of normal dermal fibroblasts. An increase in the length of the dermatan sulphate chain on decorin, a previously reported characteristic of this glycosaminoglycan in hypertrophic scar, was seen in all but two of the strains treated with transforming growth factor-β1. The depression of decorin synthesis by transforming growth factor-β1 was reversed on removal of the agent and passaging the fibroblasts. 3. The reduced capacity of fibroblasts in hypertrophic scar tissue to synthesize decorin may have implications for the development of the condition since this small proteoglycan is involved in tissue organization and may also play a role in modulating the activity in vivo of fibrogenic cytokines such as transforming growth factor-β1.

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Differential in vitro responses of elastin expression to basic fibroblast growth factor and transforming growth factor β1 in upper, middle and lower dermal fibroblasts

Archives of Dermatological Research ◽

10.1007/s004030050136 ◽

1996 ◽

Vol 288 (12) ◽

pp. 753-756 ◽

Cited By ~ 1

Author(s):

S. Tajima ◽

Tatsuya Izumi

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Basic Fibroblast Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Dermal Fibroblasts ◽

Fibroblast Growth

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Parathyroid Hormone and Transforming Growth Factor-β1 Coregulate Chondrocyte Differentiation In Vitro

Endocrine ◽

10.1385/endo:13:3:305 ◽

2000 ◽

Vol 13 (3) ◽

pp. 305-313 ◽

Cited By ~ 5

Author(s):

E. Nasatzky ◽

E. Azran ◽

D. D. Dean ◽

Barbara D. Boyan ◽

Z. Schwartz

Keyword(s):

Parathyroid Hormone ◽

Growth Factor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Chondrocyte Differentiation

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Transforming Growth Factor β1 (TGF-β1) Promotes Endothelial Cell Survival during In Vitro Angiogenesis via an Autocrine Mechanism Implicating TGF-α Signaling

Molecular and Cellular Biology ◽

10.1128/mcb.21.21.7218-7230.2001 ◽

2001 ◽

Vol 21 (21) ◽

pp. 7218-7230 ◽

Cited By ~ 145

Author(s):

Francesc Viñals ◽

Jacques Pouysségur

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Cell Survival ◽

Network Formation ◽

Egf Receptor ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

In Vitro Angiogenesis ◽

Tgf Β1

ABSTRACT Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary-like structures when stimulated with serum. Transforming growth factor β1 (TGF-β1) alone can substitute for serum and induce cell survival and tubular network formation. This TGF-β1-mediated angiogenic activity depends on phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (MAPK) signaling. We showed that specific inhibitors of either pathway (wortmannin, LY-294002, and PD-98059) all suppressed TGF-β1-induced angiogenesis mainly by compromising cell survival. We established that TGF-β1 stimulated the expression of TGF-α mRNA and protein, the tyrosine phosphorylation of a 170-kDa membrane protein representing the epidermal growth factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK. Moreover, we showed that all these TGF-β1-mediated signaling events, including tubular network formation, were suppressed by incubating TGF-β1-stimulated endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of TGF-α alone poorly stimulated angiogenesis; however, by reducing cell death, it strongly potentiated the action of TGF-β1. We therefore propose that TGF-β1 promotes angiogenesis at least in part via the autocrine secretion of TGF-α, a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

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