Halofuginone inhibits serum-stimulated pericardial tissue retraction in vitro.
We developed an in vitro model of tissue contraction in which living pericardium, in response to serum, contracted and the cells in situ expressed proliferating cell nuclear antigen (PCNA) and synthesized collagen. Here we evaluated the effects of halofuginone on these serum-stimulated pericardial tissue responses. Parietal pericardium was incubated with media containing increasing doses of halofuginone and evaluated for tissue contraction, evident by tissue curling. Proliferation was measured by MTS metabolism and PCNA expression. Furthermore, collagen synthesis was compared between samples incubated with halofuginone, cytochalasin B, cytochalasin D, aphidicolin, or cytosine arabinoside (AraC), using Masson's trichrome and the monoclonal antibody to sheep type I procollagen, SP1. D8. Halofuginone inhibited tissue contraction, cellular proliferation, and collagen synthesis in a dose-dependent manner. In contrast, cytochalasin B, cytochalasin D, aphidicolin, and AraC, shown previously to prevent cellular proliferation, did not prevent type I collagen synthesis. Halofuginone has been implicated as an agent in the prevention of wound-healing fibrosis. This study suggests that halofuginone may have an added benefit in the inhibition of pericardial tissue contraction, which appeared to be related to the synthesis of type I procollagen.
Marchion
Douglas C
DC
H. Lee Moffitt Cancer Center and Research Institute, MRC-BMTLAB, Tampa, Florida, USA.
Weber
Patricia A
PA
Lomnitski
Liat
L
Duran
Carlos M G
CM
Cheung
David T
DT
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D009929:Organ Size / Q000187:drug effects; D010496:Pericardium / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D052999:Quinazolinones; D044967:Serum / Q000378:metabolism*; D012756:Sheep; D046509:Tissue Culture Techniques / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*
D024042:Collagen Type I; D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; C010176:halofuginone