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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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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\u00a0mg\/kg or 100\u00a0mg\/kg) or vehicle administered by daily oral gavage up to 4\u00a0weeks. The prevention of bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by lanifibranor was explored.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Gene expression data were consistent with the downregulation of the PPAR pathway in the T\u03b2RII\u2206k-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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In the T\u03b2RII\u2206k-fib mouse strain, treatment with 100\u00a0mg\/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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-021-02592-x","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T08:04:39Z","timestamp":1630915479000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis"],"prefix":"10.1186","volume":"23","author":[{"given":"Emma","family":"Derrett-Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina E. 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CD reports grants and personal fees from GSK, personal fees from Boerhinger Ingelheim, grants from Servier, grants and personal fees from Inventiva, grants and personal fees from Arxx Therapeutics, personal fees from Corbus, personal fees from Sanofi and personal fees from Roche. The other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"234"}}