B. Duoto1,2, A. Moore1,3, D. Foster1, R. E. Jones1,4, S. Mascharak1, G. Wernig5, M. Longaker1 1Stanford Univserity,Surgery,Stanford, CALIFORNIA, USA 2San Jose State University,Biology,San Jose, CALIFORNIA, USA 3Brigham And Women’s HospitalBrigham And Women’s Hospital,Surgery,Boston, MASSACHUSSETTS, USA 4University Of Texas Southwestern Medical Center,Surgery,Dallas, TX, USA 5Stanford University,Pathology,Stanford, CALIFORNIA, USA
Introduction:
Fibrosis and scar formation are major clinical issues which result in disfigurement and permanent functional loss. In both adults and children, excessive fibrosis after surgery or injury can result in complications that are difficult to treat, often recur, and have few effective therapeutic options. Additionally, the only animal models that exist to simulate these processes in humans include the red Duroc pig and rabbit ear, which are expensive, difficult to use, and do not provide transgenic modeling. Recently, a paper describing a transgenic mouse strain that utilizes over-expression of c-Jun, an AP-1 transcription factor, to induce global tissue fibrosis was published. We hypothesize that local induction of c-Jun in the same transgenic mouse would result in increased scarring and fibrosis.
Methods:
Stented excisional dorsal wounding was performed on c-JuntetO; R26-M2rtTA mice along with injections of phosphate buffered saline (PBS), or with c-Jun inducing agent doxycycline at 0.1mg/mL, and 2mg/mL concentrations. Induction and dressing changes were performed every other day until wounds were completely healed. Wounds were then harvested and stained with hematoxylin and eosin for scar thickness and trichrome for collagen deposition. These assays quantify stain-specific wound characteristics.
Results:
Preliminary histological staining data uncovered a significantly increased scar thickness in the c-JuntetO R26-M2rtTA mice as compared to the C57BL/6J PBS control mice (*p<0.0001) and the C57BL/6J 2mg/mL doxycycline control mice (*p<0.0001). Comparatively, in regards to the amount of scar collagen deposition, no significance was found between the c-JuntetO R26-M2rtTA mice and the C57BL/6J PBS control mice (p=0.0832) as well as the C57BL/6J 2mg/mL doxycycline control mice (p=0.1692).
Conclusion:
Histological stains of c-JuntetO R26-M2rtTA dorsal wounds support that there are distinct differences in scar formation in the c-Jun transgenic model as compared to controls. These data support that this novel mouse model can be developed to study the molecular pathways which lead to, and inhibit, fibrosis. In future studies we will investigate novel inhibitors of fibrosis in this animal model, study the scar forming fibroblasts in greater detail, and compare our results to human specimens.
