Inhibition of lncRNA PFRL prevents pulmonary fibrosis by disrupting the miR-26a/smad2 loop
| Autor: | Yingzhun Chen, Xuelian Li, Lu Zhang, Haihai Liang, Huitong Shan, Tong Yu, Hongli Shan, Hua Jiang, Xiaoguang Zhao, Jian Sun |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Poor prognosis Physiology Pulmonary Fibrosis Smad2 Protein Transforming Growth Factor beta1 03 medical and health sciences Idiopathic pulmonary fibrosis Bleomycin Mice 0302 clinical medicine Physiology (medical) Pulmonary fibrosis Medicine Animals Lung Cells Cultured Cell Proliferation Regulation of gene expression Antibiotics Antineoplastic Cell growth business.industry Interstitial lung disease RNA Cell Biology Fibroblasts medicine.disease Mice Inbred C57BL MicroRNAs 030104 developmental biology Animals Newborn Gene Expression Regulation 030220 oncology & carcinogenesis Cancer research RNA Long Noncoding Signal transduction business Signal Transduction |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 315(4) |
| ISSN: | 1522-1504 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with increasing mortality and poor prognosis. The current understanding of the role of long noncoding RNAs (lncRNAs) in IPF remains limited. In the present study, we identified a lncRNA NONMMUT022554, designated pulmonary fibrosis-regulatory lncRNA (PFRL), with unknown functions and found that its levels were increased in fibrotic lung tissues of mice and pulmonary fibroblasts exposed to transforming growth factor (TGF)-β1. Furthermore, we found that enforced expression of PFRL induced fibroblast activation and collagen deposition, which could be mitigated by the overexpression of microRNA (miR)-26a. By contrast, the inhibition of PFRL could markedly alleviate the TGF-β1-induced upregulation of fibrotic markers and attenuate fibroblast proliferation and differentiation by regulating miR-26a. Meanwhile, our study confirmed that PFRL inhibited the expression and activity of miR-26a, which has been identified as an antifibrotic miRNA in our previous study. Interestingly, our molecular study further confirmed that Smad2 transcriptionally inhibits the expression of miR-26a and that the miR-26a/Smad2 feedback loop mediates the profibrotic effects of PFRL in lung fibrosis. More importantly, knockdown of PFRL ablated bleomycin-induced pulmonary fibrosis in vivo. Taken together, our findings indicate that lncRNA PFRL contributes to the progression of lung fibrosis by modulating the reciprocal repression between miR-26a and Smad2 and that this lncRNA may be a therapeutic target for IPF. |
| Databáze: | OpenAIRE |
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