Pathological fibroproliferation after tissue injury is harmful and may lead to organ dysfunction. Unfortunately, @entity66 remain intractable to current therapeutic strategies. Thus, new therapeutic approaches are needed. One possible approach is to promote resolution of physiological fibroproliferation that follows injury before it becomes pathological by activating apoptosis selectively in @entity75 . However, it is not known whether selective elimination of fibroblasts will prevent @entity82 or impede repair or worsen injury by eliminating topographic signals essential to organ reconstitution. To address this question, a tractable in vivo model system is needed in which fibroblasts can be targeted to undergo apoptosis at a chosen time and place. We developed @entity19 expressing HSV-TK from the type I collagen promoter to determine whether selective elimination of fibroblasts actively forming @entity75 is an effective therapeutic strategy for fibroproliferative disorders. The transgene renders fibroblasts actively forming fibrotic tissue susceptible to @entity4540 . To validate the transgenic model we examined whether administration of @entity4540 prevents the development of @entity82 in sponges implanted subcutaneously in the backs of the @entity19 . We demonstrate that fibroblasts/myofibroblasts isolated from sponges express HSV-TK protein and are selectively ablated by @entity4540 in vitro. In adult @entity19 , @entity4540 treatment attenuated the development of fibrotic tissue in the sponges both biochemically and histologically. We conclude that this transgenic model system is an ideal approach to determine whether targeted ablation of fibroblasts is an effective therapeutic strategy for @entity66 .

An HSV-TK transgenic XXXX model to evaluate elimination of fibroblasts for @entity82 therapy.

@entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity66 :: ('MESH:D004194', 'Disease') :: ['fibrotic diseases', 'fibroproliferative diseases'] @entity75 :: ('MESH:D001927', 'Disease') :: ['fibrotic lesions'] @entity19 :: ('10090', 'Species') :: ['transgenic mice'] @entity4540 :: ('MESH:D015774', 'Chemical') :: ['ganciclovir']
@entity19 :: (10090,Species) :: ['mouse']
