title: Phenytoin reduces the contraction of recessive dystrophic epidermolysis bullosa fibroblast populated collagen gels.
abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is a group of genetic disorders in which blistering occurs below the basement membrane, in many cases resulting in extensive scar formation, contractures and mitten deformities. Our aim was to compare quantitatively the contraction forces generated by normal and RDEB fibroblats and to investigate the effect of Phenytoin (5,5-diphenyl-2,4-imidazolidinedione, sodium salt; PHT). PHT is an anticonvulsant agent, that causes fibrosis as a side effect. This study utilised conventional untethered fibroblast populated collagen lattice contraction and a quantitative force measurement instrument, the culture force monitor (CFM). The RDEB cell lines were hypercontractile, generating 2.5 times the force of normal fibroblasts, though they appeared morphologically normal. In untethered collagen gels PHT (20 micrograms/ml) significantly reduced contraction of both normal and RDEB fibroblasts over 7 days. Pre-treatment of RDEB cells for 5 days also produced a 40% reduction in contraction as measured in the CFM. One suggested mechanism of PHT action is through inhibition of matrix metalloproteinase activity, but the similar effects of PHT and Colchicine (an inhibitor of microtubule polymerisation) in the CFM, indicate that it may act on contraction through disruption of microfilaments and changes to cell shape. These findings show that isolated RDEB fibroblasts retain the hypercontractile features of many of the patient's lesion sites and imply that local application of PHT may have a therapeutic effect in controlling contraction.
authors.affiliation: University College London, Division of Plastic and Reconstructive Surgery, U.K.
authors.forename: G
authors.initials: G
authors.lastname: Talas
authors.forename: T S
authors.initials: TS
authors.lastname: Adams
authors.forename: M
authors.initials: M
authors.lastname: Eastwood
authors.forename: G
authors.initials: G
authors.lastname: Rubio
authors.forename: R A
authors.initials: RA
authors.lastname: Brown
mesh_terms: D001696:Biomechanical Phenomena; D002460:Cell Line; D003094:Collagen; D003286:Contracture / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005782:Gels; D006801:Humans; D010672:Phenytoin / Q000494:pharmacology*
chemical_list: D005782:Gels; D010672:Phenytoin; D003094:Collagen