A small interfering RNA inhibits lung fibroblast-myofibroblast differentiation via simultaneously knockingdown CELF1 and activating RIG-I signalling

Abstract

Fibroblast-myofibroblast differentiation plays a key role in the pathogenesis of pulmonary fibrosis. Integrating RNA interference and RNA immunostimulation functions to treat diseases is a promising new potential therapy. Here, we report that an elevated expression of CUGBP Elav-Like Family Member 1 (CELF1), an RNA-binding protein, positively correlates with lung fibroblast-myofibroblast differentiation in fibrotic lung tissues. Knockdown of CELF1 expression by siRNA-17834 or siRNA-116447 inhibited lung fibroblast-myofibroblast differentiation via promoting the anti-fibrotic IL7 mRNA stability. Interestingly, siRNA-17834 but not siRNA-116447 unexpectedly induced Retinoic Acid-inducible Gene I (RIG-I) dependent IFN-β production, which also inhibited lung fibroblast-myofibroblast differentiation. In conclusion, siRNA-17834 has dual functions of RNA interference and RNA immunostimulation to control lung fibroblast-myofibroblast differentiation, which suggests a novel strategy for the treatment of pulmonary fibrosis.