LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation

• DOI: 10.1016/j.apsb.2022.04.006
• Publication Date: 2022-04-16T05:49:42Z
• Authors: Jian Sun; Tongzhu Jin; Zhihui Niu; Jiayu Guo; Yingying Guo; Ruoxuan Yang; Qianqian Wang; Huiying Gao; Yuhan Zhang; Tianyu Li; Wenxin He; Zhixin Li; Wenchao Ma; Wei Su; Liangliang Li; Xingxing Fan; Hongli Shan; Haihai Liang
• Keywords: Myofibroblast

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts prominent feature fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) downregulated in the lungs IPF patients an experimental mouse model lung LncDACH1 knockout mice develop spontaneous fibrosis, whereas overexpression attenuated TGF-β1-induced aberrant activation, collagen deposition differentiation fibroblasts. Similarly, forced expression not only prevented bleomycin (BLM)-induced but also reversed established BLM model. Mechanistically, binding to serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity inhibits accumulation Ctnnb1. Enhanced SRSF1 blocked anti-fibrotic effect Furthermore, loss promoted proliferation, differentiation, extracellular matrix (ECM) fibroblasts, such effects were abolished by silencing In addition, conserved fragment alleviated hyperproliferation, ECM MRC-5 cells driven TGF-β1. Collectively, interacting suppress CTNNB1 accumulation, suggesting might be potential target for