Runx1 promotes pulmonary fibrosis through fibroblasts differentiation and senescence

<bold>Background:</bold> Lung fibrosis is an abnormal repair process following injury response and characterized by fibroblasts activation and excessive extracellular matrix (ECM) deposition。Recent studies suggest Runt-related transcription factor 1 (RUNX1) involved in lung fibrosis. In this study we determined how RUNX1 influenced fibroblast. <bold>Methods:</bold> RUNX1 was detected in IPF patients and bleomycin (BLM)-induced pulmonary fibrosis mice model. ECM were detected after adenovirus or silence RNA was used to overexpressed/inhibited Runx1 with or without RUNX1 inhibitor Ro5-3335 or TGF-β treatment. Fibroblasts proliferation, migration, and senescence were investigated. Runx1 inhibitor Ro5-3335 was also conducted in mice model. <bold>Results:</bold> RUNX1 are increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of RUNX1 are related to worse lung function. Additionally, RUNX1 was highly identified in lung fibroblasts by scRNA-Seq analysis and confirmed in IPF tissue and BLM mice lung tissue by immunofluorescence staining. Further investigation showed RUNX1 promoted fibroblast differentiation and senescence, while having no effect on proliferation and migration (Figure 1). More importantly, Ro5-3335, a RUNX1 inhibitor, was effective at reversing established pulmonary fibrosis <italic>in vivo</italic> (Figure 2). <bold>Conclusion</bold>: Runx1 plays a pivotal role in mediating fibroblast differentiation and senescence. Runx1 inhibitor Ro5-3335 might be a promising therapeutic approach for the treatment of pulmonary fibrosis.