Analysis of gene expression in canine idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) in dogs is a rare disease of unknown aetiology, seen in terrier breeds, particularly the West Highland white terrier (WHWT). The aim of this study was to determine pulmonary gene expression in canine IPF in order to gain insights into the pathogenesis of the disease and to identify possible biomarkers. Microarray analyses were conducted to determine gene expression profiles in the lungs of dogs with IPF and control dogs of various breeds. More than 700 genes were identified as having greater than two-fold difference in expression between the two groups. The significant biological functions associated with these genes were related to cellular growth and proliferation, developmental processes, cellular movement, cell to cell signalling and interaction, and antigen presentation. Altered levels of expression were confirmed by quantitative reverse transcriptase PCR for genes encoding chemokine (C-C) ligand (CCL) 2 (+4.9 times), CCL7 (+6.8 times), interleukin 8 (+4.32 times), chemokine (C-X-C) ligand 14 (+3.4 times), fibroblast activation protein (+4.7 times) and the palate, lung and nasal associated protein (PLUNC, -25 times). Serum CCL2 concentrations were significantly higher in WHWTs with IPF (mean 628.1 pg/mL, interquartile range 460.3-652.7 pg/mL) than unaffected WHWTs (mean 344.0 pg/mL, interquartile range 254.5-415.5 pg/mL; P=0.001). The results support CCL2 as a candidate biomarker for IPF in dogs.