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5-fluorouracil selectively inhibits collagen synthesis
Neil W Bulstrode1, Vivek Mudera, D Angus McGrouther
1RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Middlesex, United Kingdom.
Plastic and Reconstructive Surgery
|July 1, 2005
Summary
5-Fluorouracil selectively reduced collagen production in Dupuytren
Area of Science:
- Biochemistry
- Cell Biology
- Dermatology
Background:
- Fibroproliferative disorders involve excessive collagen production.
- 5-Fluorouracil (5-FU) treats fibroproliferative disorders by inhibiting DNA replication.
- 5-FU down-regulates fibroblast proliferation and differentiation in vitro.
Purpose of the Study:
- To investigate the dose-dependent effect of 5-FU on fibroblast extracellular matrix production.
- To assess 5-FU's impact on collagen synthesis and TGF-beta1 secretion in Dupuytren's fibroblasts.
Main Methods:
- Fibroblasts from Dupuytren's disease and tendon were cultured.
- Collagen synthesis was measured using radiolabeled proline.
- TGF-beta1 secretion and gene expression of collagen and TGF-beta1 were quantified.
Main Results:
- 5-FU decreased collagen production in a dose-dependent manner.
- Collagen mRNA levels (types I and III) were not affected by 5-FU.
- Changes in collagen production were independent of TGF-beta1 secretion.
Conclusions:
- 5-Fluorouracil may reduce extracellular matrix production.
- This suggests a potential role for 5-FU in reducing Dupuytren's disease recurrence.