RESUMEN
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFbeta1 as a key effector cytokine in the development of lung fibrosis. METHODS: In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFbeta1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically. RESULTS: The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFbeta1 associated pulmonary fibrosis. CONCLUSION: This data emphasises the importance of a host predisposition in the form of endogenous TGFbeta1, in the development of pulmonary fibrosis in response to an exogenous injury.
RESUMEN
Wound healing in adult mammals proceeds by a series of overlapping highly coordinated events. Dermal wound repair commences with the arrest of hemorrhage followed by an inflammatory response, re-epithelialization of the wound, and formation of granulation tissue within the wound space, culminating in the production of a scar. In order to study the processes involved in the repair of wounded tissue, we have developed a rodent model utilizing full thickness incisional and excisional dermal wounds, which allow for macroscopic observations and also provide tissue for the histological and immunocytochemical analysis of acute wounds and scarring.
