Introduction RNA binding proteins (RBPs) associate with RNAs to regulate all aspects of mRNA biogenesis and metabolism. Their complex role remains poorly understood in lung diseases. Idiopathic pulmonary fibrosis (IPF) is a life-threatening chronic lung disease that is characterized by alveolar epithelial cell injury and severe fibroblast proliferation and ultimately fibrosis.

Aim The goal here was to understand the pathological role of RBPs in lung fibrosis.

Methods Explanted lungs and interstitial fibroblasts from IPF patients or donors, in vivo and in vitro models for amiodarone induced lung fibrosis were exploited. Precision cut lung slices (PCLS) from IPF lungs treated with the standard of care drug, pirfenidone (Pirf) were analyzed. Results Differential regulation of several RBPs including TAR DNA binding protein 43 kDa, fused in sarcoma (FUS), muscleblind like splicing regulator 1 and polyadenylate-binding protein 1 (PABPC1) were observed in IPF and in the amiodarone model. FUS and PABPC1 were increased in the interstitial fibroblasts in IPF. Overexpression of FUS in healthy primary fibroblasts resulted in an increase in proliferating cell nuclear antigen (PCNA), indicating that increased FUS alone is sufficient to trigger enhanced proliferation. In human IPF PCLS treated with pirfenidone, a decreased staining for both, FUS and PABPC1, was observed indicating that its anti-fibrotic effects may, at least in part, be mediated by targeting of RBPs.

Conclusions Our study shows strict cell specific altered expression and localization of RBPs in IPF patient lungs. Therapeutic targeting of RBPs may hence prove beneficial for IPF but needs to be studied in more detail.