Reduction in dermal fibrosis in the tight-skin (Tsk) mouse after local application of halofuginone

Mark Pines*, Avraham Domb, Meir Ohana, Jacob Inbar, Olga Genina, Rosaly Alexiev, Arnon Nagler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The effect of dermal application of halofuginone - an inhibitor of collagen type I synthesis - on skin collagen and collagen α1(I) gene expression in an animal model of scleroderma and chronic graft versus host disease (cGvHD) was evaluated. Halofuginone-containing cream was applied on the tight-skin mouse (Tsk) and skin biopsies were taken for collagen staining by sirius red and for collagen α1(I) gene expression by in situ hybridization. In addition, cell proliferation was evaluated by immunostaining for proliferation cell nuclear antigen (PCNA) alone or in combination with collagen α1(I) probe. The number of mast cells was assessed by toluidine blue. Dermal application of halofuginone (0.01%) for 60 days was as good as systemic administration (1 μg/mouse/day) in reducing collagen α1(I) gene expression in skin biopsy and almost as good in reducing skin width. Halofuginone was stable and effective only at acidic pH. The effect of halofuginone (0.03%) was time-dependent. After 40 days of daily treatment, a significant reduction in the collagen α1(I) gene expression was observed and further decrease was observed after 60 days. The reduction in collagen α1(I) gene expression and the reduction in the proliferation of dermal fibroblasts probably occur in the same subset of cells. No effect of halofuginone on the proliferation of keratinocytes or on mast cell number was observed. These results suggest that target-oriented application of halofuginone may become a novel therapy for fibrotic disorders in general and for scleroderma in particular.

Original languageEnglish
Pages (from-to)1221-1227
Number of pages7
JournalBiochemical Pharmacology
Issue number9
StatePublished - 1 Nov 2001
Externally publishedYes


  • Collagen type I
  • Extracellular matrix
  • Fibrosis
  • Scleroderma


Dive into the research topics of 'Reduction in dermal fibrosis in the tight-skin (Tsk) mouse after local application of halofuginone'. Together they form a unique fingerprint.

Cite this