Calcium-Sensing Receptor Antagonism as a Novel Therapeutic for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disease with poor prognosis and no curative therapies. Fibroblast activation by transforming growth factor b1 (TGFb1) and disrupted metabolic pathways, including the arginine-polyamine pathway, play crucial roles in IPF development. Polyamines are agonists at the calcium/cation-sensing receptor (CaSR), activation of which is detrimental for asthma and pulmonary hypertension, but its role in IPF is unknown. We assessed the anti-fibrotic effects of a CaSR antagonist, NPS2143, in TGFb1-activated normal primary human lung fibroblasts by RNA sequencing