Idiopathic pulmonary fibrosis (IPF) is a complex interstitial lung disease characterized by chronic, progressive scarring of the lung thought to be triggered by ongoing epithelial injury. The etiology and pathogenic mechanisms underlying IPF are largely unknown, and despite intensive research, effective therapies have not been developed. Exposure to environmental agents in genetically susceptible individuals is thought to underlie development of IPF. Thus, to investigate gene x environment interactions in pulmonary fibrosis, we developed a mouse model of interstitial pulmonary fibrosis using vanadium pentoxide (V2O5), a transition metal found in ambient particulate matter and certain occupational settings. Haplotype mapping and genetic linkage analysis of V2O5-induced lung collagen content in mice identified several quantitative trait loci (QTL) and candidate susceptibility genes.
Our laboratory is currently further characterizing the V2O5-induced interstitial pulmonary fibrosis model and investigating the role of novel candidate susceptibility genes identified in QTLs.
1. Characterization of the V2O5-induced interstitial pulmonary fibrosis model in mice. The lack of mechanistic understanding and effective therapies for IPF is partially attributed to the fact that animal models of pulmonary fibrosis do not closely mimic the human disease. We are investigating whether the V2O5 model is an improvement over other commonly used models in regard to progression and stability of fibrosis, histologic pattern of IPF, and biomarkers of fibrosis.
2. Candidate susceptibility genes for fibrosis.