A novel tree shrew model of pulmonary fibrosis.
Pulin CheMeimei WangJennifer L Larson-CaseyRui-Han HuYiju ChengMustapha El HamdaouiXue-Ke ZhaoRafael GrytzA Brent CarterQiang DingPublished in: Laboratory investigation; a journal of technical methods and pathology (2020)
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease without effective therapy. Animal models effectively reproducing IPF disease features are needed to study the underlying molecular mechanisms. Tree shrews are genetically, anatomically, and metabolically closer to humans than rodents or dogs; therefore, the tree shrew model presents a unique opportunity for translational research in lung fibrosis. Here we demonstrate that tree shrews have in vivo and in vitro fibrotic responses induced by bleomycin and pro-fibrotic mediators. Bleomycin exposure induced lung fibrosis evidenced by histological and biochemical fibrotic changes. In primary tree shrew lung fibroblasts, transforming growth factor beta-1 (TGF-β1) induced myofibroblast differentiation, increased extracellular matrix (ECM) protein production, and focal adhesion kinase (FAK) activation. Tree shrew lung fibroblasts showed enhanced migration and increased matrix invasion in response to platelet derived growth factor BB (PDGF-BB). Inhibition of FAK significantly attenuated pro-fibrotic responses in lung fibroblasts. The data demonstrate that tree shrews have in vivo and in vitro fibrotic responses similar to that observed in IPF. The data, for the first time, support that the tree shrew model of lung fibrosis is a new and promising experimental animal model for studying the pathophysiology and therapeutics of lung fibrosis.
Keyphrases
- idiopathic pulmonary fibrosis
- extracellular matrix
- growth factor
- transforming growth factor
- pulmonary fibrosis
- interstitial lung disease
- systemic sclerosis
- epithelial mesenchymal transition
- multiple sclerosis
- cell migration
- stem cells
- machine learning
- escherichia coli
- small molecule
- pseudomonas aeruginosa
- diabetic rats
- mesenchymal stem cells
- staphylococcus aureus
- liver fibrosis
- signaling pathway
- biofilm formation