CEBPB promotes the development of pulmonary arterial hypertension by transforming smooth muscle cell into myofibroblast

Myofibroblast promotes pulmonary vascular remodeling by secreting extracellular matrix and enhancing fibrosis, leading to pulmonary arterial hypertension (PAH). We analyzed single cell sequencing data of lung tissues from PAH and control groups in GEO database and identified myofibroblast from smooth muscle cell (SMC). By comparing transcriptomic profiles of SMC and myofibroblast with SCENIC, We found that CEBPB may regulate marker genes in the transformation of SMC into myofibroblast. Besides, the protein levels of CEBPB in PAH was increasing. Knockdown of CCAAT box enhancer binding protein-B (CEBPB) inhibited the abnormal proliferation and migration of PASMC from PAH rats or under hypoxia, accompanied by downregulation of fibroblast related marker genes in PASMC. Subsequently, we achieved smooth muscle specific knockdown of CEBPB by injecting adeno-associated virus (AAVs) carrying CEBPB siRNA into Tagln-cre heterozygote mouse 2 weeks before constructing PAH model. Smooth muscle specific knockdown of CEBPB significantly alleviated lung tissue and pulmonary vascular fibrosis of PAH models. Further more, smooth muscle specific knockdown of CEBPB decreased right ventricular systolic pressure and inhibited pulmonary vascular remodeling. The current study reveals the regulatory role of CEBPB in PAH and provide novel insights into the pathogenesis of PAH.