An experimental mouse model of lung fibrosis

Abstract

Pulmonary fibrosis is a pathologic chronic lung disorder characterized by the deposition of extracellular matrix and damage to lung architecture. Models of pulmonary fibrosis were developed in several animal species. However, murine models are more common due to their low costs, availability and well characterized immune systems. Indeed, these murine models play an important role in understanding the biology of the diseases, deciphering the cellular and molecular mechanisms mediating pulmonary pathobiology and to explore novel therapeutic approaches. Although the majority of these models mimic certain characteristics of human idiopathic pulmonary fibrosis, most of them do not mimic other features especially those related to the progressive and irreversible nature of this disease. The present protocol describes the induction of a pulmonary fibrosis model in mice with bleomycin, which is a risk factor for human lung fibrosis. Specifically, we described the methodology of intratracheal instillation of bleomycin as well as the assessment methods of pulmonary fibrosis either histopathologically based on Ashcroft grading score or by quantitatively based on biochemical biomarkers. Moreover, we proposed a detailed readout that can determine the degree of lung injury in bronchoalveolar lavage fluids. We described different cellular and molecular markers such as by total protein concentration, total cell count, immune cell differential count, and the expression of pro-inflammatory mediators. We present this model as a reference for studies on the pulmonary fibrosis.