LncRNA protects against pulmonary fibrosis by binding to SRSF1 to suppress accumulation.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of attenuated TGF-1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of . Enhanced expression of SRSF1 blocked the anti-fibrotic effect of in lung fibroblasts. Furthermore, loss of promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of . In addition, a conserved fragment of alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-1. Collectively, inhibits lung fibrosis by interacting with SRSF1 to suppress accumulation, suggesting that might be a potential therapeutic target for pulmonary fibrosis.