BACKGROUND: The TβRII∆k-fib transgenic (TG) mouse model of scleroderma 
replicates key fibrotic and vasculopathic complications of systemic sclerosis 
through fibroblast-directed upregulation of TGFβ signalling. We have examined 
peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this 
model and explored the impact of the pan-PPAR agonist lanifibranor on the 
cardiorespiratory phenotype.
METHODS: PPAR pathway gene and protein expression differences from TG and WT 
sex-matched littermate mice were determined at baseline and following 
administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or 
vehicle administered by daily oral gavage up to 4 weeks. The prevention of 
bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by 
lanifibranor was explored.
RESULTS: Gene expression data were consistent with the downregulation of the 
PPAR pathway in the TβRII∆k-fib mouse model. TG mice treated with high-dose 
lanifibranor demonstrated significant protection from lung fibrosis after 
bleomycin and from right ventricular hypertrophy following induction of 
pulmonary hypertension by SU5416, despite no significant change in right 
ventricular systolic pressure.
CONCLUSIONS: In the TβRII∆k-fib mouse strain, treatment with 100 mg/kg 
lanifibranor reduces the development of lung fibrosis and right ventricular 
hypertrophy induced by bleomycin or SU5416, respectively. Reduced PPAR activity 
may contribute to the exaggerated fibroproliferative response to tissue injury 
in this transgenic model of scleroderma and its pulmonary complications.