lncITPF Promotes Pulmonary Fibrosis by Targeting hnRNP-L Depending on Its Host Gene ITGBL1

Abstract

The role of long non-coding RNA (lncRNA) in idiopathic pulmonary fibrosis (IPF) is poorly understood. We found a novel lncRNA-ITPF that was upregulated in IPF. Bioinformatics and in vitro translation verified that lncITPF is an actual lncRNA, and its conservation is in evolution. Northern blot and rapid amplification of complementary DNA ends were used to analyze the full-length sequence of lncITPF. RNA fluorescence in situ hybridization and nucleocytoplasmic separation demonstrated that lncITPF was mainly located in the nucleus. RNA sequencing, chromatin immunoprecipitation (ChIP)-qPCR, CRISPR-Cas9 technology, and promoter activity analysis showed that the fibrotic function of lncITPF depends on its host gene integrin b-like 1 (ITGBL1), but they did not share the same promoter and were not co-transcribed. Luciferase activity, pathway inhibitors, and ChIP-qPCR showed that smad2/3 binds to the lncITPF promoter, and TGF-b1-smad2/3 was the upstream inducer of the fibrotic pathway. Furthermore, RNA-protein pull-down, liquid chromatography-mass spectrometry (LC-MS), and protein-RNA immunoprecipitation showed that lncITPF regulated H3 and H4 histone acetylation in the ITGBL1 promoter by targeting heterogeneous nuclear ribonucleoprotein L. Finally, sh-lncITPF was used to evaluate the therapeutic effect of lncITPF. Clinical analysis showed that lncITPF is associated with the clinicopathological features of IPF patients. Our findings provide a therapeutic target or diagnostic biomarker for IPF.

Angelica Sinensis Polysaccharide Suppresses Epithelial-Mesenchymal Transition and Pulmonary Fibrosis via a DANCR/AUF-1/FOXO3 Regulatory Axis

“…Previous studies revealed that lncRNAs participate in various cellular processes and that the dysregulation of lncRNAs usually leads to the o development of diseases, such as cancer [14] and cardiovascular diseases [15]. Moreover, several studies indicated that certain lncRNAs, such as PFAR [16], lncITPF [17], PFRL [18] and PFAL [19], act as important regulators in the progression of IPF. However, the exact functions of lncRNAs in IPF remain elusive.…”

Engeletin ameliorates pulmonary fibrosis through endoplasmic reticulum stress depending on lnc949-mediated TGF-β1-Smad2/3 and JNK signalling pathways

“…We previously identified the action mechanism of lncITPF in IPF progression and proposed that lncITPF can be a potential therapeutic target or diagnostic biomarker for IPF (Song et al. 2019 ). We also proved that lncRNA-NUNMM028949.2 can serve as a new therapeutic drug target in pulmonary fibrosis (Zhang et al.…”

Decrypting the crosstalk of noncoding RNAs in the progression of IPF

“…In fibroblasts, lncRNA RP11-413M3.4 promotes the upregulation of the adjacent gene Notch1, induces the proliferation and differentiation of myofibroblasts and produces a large amount of collagen fibers, leading to pulmonary fibrosis [11]. Song et al [12] indicated that lncITPF can increase the expression of its nearby host gene, Itgbl1, through TGF-β1. The expression of lncRNA AP003419.16 and its adjacent gene RPS6KB2, increased significantly in patients with IPF.…”