ISSN: 0970-938X (Print) | 0976-1683 (Electronic)
An International Journal of Medical Sciences
Roopa Biswas, Parameet Kumar, Raymond A Frizzell and Harvey B Pollard
Uniformed Services University of the Health Sciences, USA
University of Pittsburgh, USA
Scientific Tracks Abstracts : Biomed Res
DOI: 10.4066/biomedicalresearch-C1-002
Cystic fibrosis (CF) is the most common life limiting recessive disease in the US and is due to mutations in the CFTR gene. CF mutations, of which the most common is F508del-CFTR, cause a massive pro-inflammatory phenotype in the lung arising from dysregulated expression of inflammatory genes. Recently, endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs) have emerged as important targets in the frontier of biomedical research. These ncRNAs coordinate with epigenetic factors to play a crucial role in the regulation of biological processes as well as in diseases. Long noncoding RNAs (LncRNAs) have emerged as novel regulators of gene expression, including inflammatory genes. Various diseases have been associated with the aberrant expression of LncRNAs. Here we report the role of LncRNA and associated epigenetic factors in the pathogenesis of CF lung disease. LncRNA nuclear enriched abundant transcript 1 (NEAT1) is aberrantly upregulated in CF cells including, IB3- 1, CFPAC-1 and CFBE CF cells as well as in lung tissues of CF patients compared to the respective control cells. NEAT1 has been shown to regulate the expression of pro-inflammatory cytokine IL-8 in other diseases. Consistently, we find that suppression of NEAT1 in CF lung epithelial cells leads to reduced expression of IL-8. Additionally, NEAT1 is induced by p38- MAPK signaling pathway, which is activated in CF, and our results indicate that inhibition of this pathway suppresses both NEAT1 as well as IL-8. Our data indicate that SFPQ, a NEAT1 interacting protein, is down-regulated in F508del-CFTR CF lung epithelial cells compared to WT-CFTR control cells and perhaps also contributing to increased expression of IL-8. Consistently, we find that increased exogenous expression of SFPQ not only attenuates expression of the pro-inflammatory IL-8 gene, suppresses pro-fibrotic CTGF protein, but also rescues F508del- CFTR expression in CF lung epithelial cells. Understanding these mechanisms will lead to novel therapeutic targets for CF and related pulmonary diseases. Chronic diseases and even aging itself are known to damage the body by dys-regulated inflammatory processes. Dysregulated expression of the pro-inflammatory cytokine and chemokine genes are known to contribute to chronic inflammatory diseases. Recently, endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs) and microRNAs (miRNAs, miRs) have emerged as important targets in the frontier of biomedical research. These non-coding RNAs have been proven to be key regulators of gene expression. The ability to detect non-coding RNAs in biofluids has highlighted their usefulness as non-invasive markers of diseases, including lung diseases. The expression of specific noncoding RNAs is altered in many lung diseases and their levels in the circulation often reflect the changes in expression of their lungspecific counterparts. Therefore, exploiting these biomolecules as diagnostic tools seems an obvious goal. Our goal is to investigate the role of non-coding RNAs in Cystic Fibrosis lung disease and develop novel anti-inflammatory therapeutics for pulmonary disorders.
Roopa Biswas is an Associate Profeesor in Anatomy, Physiology and Gentics Department in University of Health Science, USA.
E-mail: roopa.biswas@usuhs.edu
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