Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis

Abstract

Abstract. Recent studies suggest that long non-coding RNAs (lncRNAs) are more involved in human diseases than previously realized. A growing body of evidence links lncRNA mutation and dysregulation to diverse human diseases. However, the association of lncRNAs with the pathogenesis of lung fibrosis remains poorly understood. In this study, we detected changes in hydroxyproline and collagen levels, as well as the ultrastructure of lung tissue to develop a rat model of lung fibrosis. The differentially expressed lncRNAs and mRNA profiles between fibrotic lung and normal lung tissue were analyzed using microarrays. Gene Ontology analysis and pathway analysis were performed for further research. Two differentially expressed lncRNAs, namely, AJ005396 and S69206, were detected by in situ hybridization to validate the microarray data. The results revealed that the number of collagen fibers in the interstitial lung tissue significantly increased in the model group compared with the normal group. In total, 210 and 358 lncRNAs were upregulated and downregulated, respectively, along with 415 upregulated and 530 downregulated mRNAs in the rats with lung fibrosis. AJ005396 and S69206 were upregulated in the fibrotic lung tissue, consistent with the microarray data, and were located in the cytoplasm of the interstitial lung cells. In conclusion, the expression profile of the lncRNAs was significantly altered in the fibrotic lung tissue and these transcripts are potential molecular targets for inhibiting the development of lung fibrosis. IntroductionIdiopathic pulmonary fibrosis (IPF) is a common, chronic, progressive and usually lethal fibrotic lung disease with poor prognosis (1). This disease is characterized by focal areas of alveolar epithelial cell injury and the excessive proliferation of mesenchymal cells in the interstitium, which results in the excessive deposition of extracellular matrix (ECM) and distorted architecture leading to impaired gas exchange (2,3). Although many pathobiological concepts are emerging, including the role of aging and cellular senescence, oxidative stress, endoplasmic reticulum stress, cellular plasticity, microRNA (miRNA) and mechanotransduction, the molecular mechanisms behind IPF are not yet completely understood (4).The Encyclopedia of DNA Elements (ENCODE) project, which aimed to comprehensively characterize the human genome, has shown that >90% of the genome has been transcribed; however, only 1-2% of that is composed of genes (5). The majority of these transcripts are not translated into proteins and are, therefore, termed non-coding RNAs (ncRNAs).Long non-coding RNAs (lncRNAs), a type of ncRNA, vary in size from 200 bp to >100 kb, and are transcribed by RNA polymerase II (6). They play an important role in imprinting (7), enhancing various biological functions (8), X chromosome inactivation (9), chromatin structure (10) and genomic rearrangement during the generation of antibody diversity (11). Thus, lncRNAs are critical for normal development and, in many cases, are deregulated in d...

The code of non-coding RNAs in lung fibrosis

“…A recent study by Lv et al identified a large number of lncRNAs that have altered expression in the lungs of rat with experimental fibrosis. This was the first piece of evidence suggesting the participation of lncRNAs in the pathogenesis of pulmonary fibrosis [48]. Among these lncRNAs, several have been previously studied in different biological settings, such as H19, RNA component of mitochondrial RNA processing endoribonuclease (RMRP), and telomerase RNA component (TERC) [103–106].…”

The expression profiling and ontology analysis of noncoding RNAs in peritoneal fibrosis induced by peritoneal dialysis fluid

“…They have been shown to exert comprehensive effects on biological processes through a variety of mechanisms (Mercer et al, 2009;Hu et al, 2012) and are thought to play important roles in the pathophysiology of several diseases, including cancer, pulmonary fibrosis and cardiovascular disease (Cao et al, 2013;Yang et al, 2013;Liu et al, 2014). Moreover, in recent studies, lncRNAs have been discovered that can act as competitive endogenous RNAs (ceRNA) of miRNAs by sharing common miRNA response elements (MREs), inhibiting miRNA activity and attenuating the repression of miRNA-target genes (Ebert and Sharp, 2010;Poliseno et al, 2010;Cesana et al, 2011).…”

All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-β1/Smad3 signaling pathway in rats

“…Hyp level in the hydrolysates was colorimetrically determined by absorbance at 560 nm with p-dimethylaminobenzaldehyde and expressed as mg/g wet tissue. 23 Immunofluorescence Rabbit anti-rat a-SMA and anti-E-cadherin antibodies were purchased from Boster Bio-engineering (Wuhan city, China). Immunofluorescence staining was performed as previously described.…”