Pulmonary arterial hypertension (PAH) is a severe vascular complication of systemic sclerosis (SSc), with interleukin-13 (IL-13) emerging as a key mediator of its pathogenesis. This project aims to elucidate the molecular mechanisms by which IL-13 promotes pulmonary vascular remodeling, particularly the hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Using an in vitro screening approach, we will identify natural compounds capable of inhibiting IL-13-induced PASMC proliferation. Additionally, we will develop and characterize an IL-13-driven ex vivo PAH model using precision-cut lung slices (PCLS). Promising natural compounds and monoclonal antibodies targeting IL-13 signaling pathways will then be evaluated for therapeutic efficacy in both ex vivo and in vivo models of SSc-associated PAH. The findings are expected to advance our understanding of IL-13-driven vasculopathy and support the development of novel treatments for PAH in SSc patients.