Unravelling the role of sFRP2 in the pathogenesis of Idiopathic Pulmonary Fibrosis

Today there is an amenable need for more effective therapeutic targets in Idiopathic Pulmonary Fibrosis. Through a machine learning pipeline using Fibromine, a multi-omics database, soluble Frizzled related protein 2 (sFRP2) was strongly suggested to have a role in IPF pathogenesis. sFRP2 is a protein that can bind to WNT ligands modulating WNT signaling pathway activity. The aim of the study is to investigate the role of sFRP2 in pulmonary fibrosis pathogenesis. 3T3-mouse embryonic fibroblasts and primary mouse lung fibroblasts were treated with TGF-β (10 ng/ml) or lysophosphatidic acid LPA (10μΜ) or vehicle and starved for 24h. sFRP2 mRNA and protein levels were analyzed by Q-RT-PCR and western blot. Bleomycin (BLM) induced pulmonary fibrosis mouse model was also used. sFRP2 was tested by immunohistochemistry in lung tissue obtained from mice 14 days after receiving BLM. TGF-β and LPA reduces the expression of sFRP2 levels in 3T3-mouse embryonic fibroblasts. Also, in primary mouse lung fibroblasts sFRP2 mRNA and protein levels were downregulated upon TGF-β. Results for all genes were found statistically significant with Welch’s t-test. sFRP2 protein exhibits predominant expression in fibrotic regions in the lung tissue of a BLM induced mouse model, where as its expression is minimal in the bronchial epithelium. <bold>Conclusion:</bold> RNA-seq and single cell data indicate increased expression of SFRP2 mRNA levels in IPF. TGF-β and LPA seem to reduce sFRP2 levels in vitro in primary mouse lung and embryonic fibroblasts. Immunohistochemistry reveals that sFRP2 is mostly located in fibrotic areas in lungs post BLM. Our data supports a promising potential role for sFRP2 in the pathogenesis of IPF.