Searching for airways biomarkers useful to identify progressive pulmonary fibrosis
Piera Soccio1, Giorgia Moriondo2, Giulia Scioscia2,3
1Department of Medical and Surgical Sciences, University of Foggia, Viale Luigi Pinto, 1, Foggia, 71122, Italy. piera.soccio@unifg.it.
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with unknown etiology. To date, the identification of new diagnostic, prognostic and progression biomarkers of IPF turns out to be necessary. MicroRNA (miRNA) are small non-coding RNAs which negatively regulate gene expression at the post-transcriptional level in several biological and pathological processes. An aberrant regulation of gene expression by miRNA is often associated with various diseases, including IPF. As result, miRNAs have emerged as potential biomarkers with relevance to pulmonary fibrosis. Several reports suggested that miRNAs are secreted as microvesicles or exosome, and hance they are stable and can be readily detected in the circulation. In the contest of miRNAs as circulating biomarkers, different studies show their role in various types of interstitial lung diseases and suggest that these small molecules could be used as prognostic markers of the disease. Exosomes are small, lipid-bound vesicles able to carry various elements of the naïve cells such as proteins, lipids, mRNAs and miRNA to facilitate cell communication under normal and diseases condition. Exosomal miRNAs (exo-miRNA) have been studied in relation to many diseases. However, there is little or no knowledge regarding exo-miRNA in bronchoalveolar lavage (BAL) in IPF. Our study's aim is to evaluate the changes in the expression of two exo-miRNAs in BAL, respectively miR-21 and miR-92a, through highlighting the differences between IPF, progressive pulmonary fibrosis (PPF) and not-progressive pulmonary fibrosis (nPPF).
Methods:
Exosomes were characterized by Western Blot and Multiplex Surface Marker Analysis. Exosomal miRNA expression was performed by qRT-PCR. ANOVA or Kruskal-Wallis test, based on data normality, was used to compare the differential expression between groups.
Results:
MiR-21 expression was significantly higher in the nPPF group than in both IPF and PPF. A result that could point above a possible role of miR-21, as a biomarker in the differential diagnosis between PPF and nPPF. MiR-92a, indeed, was down regulated in PPF compared to IPF and down regulated in PPF compared to nPPF.
Conclusions:
This study demonstrated the putative role of both miR-21 and miR-92a as possible biomarkers of pulmonary fibrosis progression. Moreover, the role of exo-miRNAs is examined as a possible future direction that could lead to new therapeutic strategies for the treatment of progressive and non-progressive pulmonary fibrosis.
Insights
Idiopathic pulmonary fibrosis (IPF) progression may be identified using exosomal microRNAs (miRNAs) in bronchoalveolar lavage. MiR-21 and miR-92a show differential expression, suggesting their potential as biomarkers for disease progression.
Area of Science:
- Pulmonology
- Biochemistry
- Molecular Biology
Background:
- Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unknown causes, necessitating new biomarkers for diagnosis and prognosis.
- MicroRNAs (miRNAs) are implicated in disease pathogenesis and, when encapsulated in exosomes, are stable circulating biomarkers.
- Exosomal miRNAs (exo-miRNAs) in bronchoalveolar lavage (BAL) for IPF are understudied, highlighting a gap in understanding their role.
Purpose of the Study:
- To investigate the expression levels of exosomal miR-21 and miR-92a in the BAL of patients with IPF.
- To differentiate expression patterns between IPF, progressive pulmonary fibrosis (PPF), and non-progressive pulmonary fibrosis (nPPF).
- To evaluate the potential of these exo-miRNAs as biomarkers for pulmonary fibrosis progression.
Main Methods:
- Exosomes were isolated and characterized using Western Blot and Multiplex Surface Marker Analysis.
- Exosomal miRNA expression was quantified via quantitative real-time PCR (qRT-PCR).
- Statistical analysis (ANOVA or Kruskal-Wallis) was employed to compare differential expression between patient groups.
Main Results:
- MiR-21 expression was significantly higher in the nPPF group compared to both IPF and PPF groups, suggesting a role in differential diagnosis.
- MiR-92a was found to be downregulated in the PPF group relative to both the IPF and nPPF groups.
- These findings indicate distinct expression profiles for miR-21 and miR-92a in different stages of pulmonary fibrosis.
Conclusions:
- Exosomal miR-21 and miR-92a show potential as biomarkers for assessing pulmonary fibrosis progression.
- Further research into exo-miRNAs could pave the way for novel therapeutic strategies for IPF.
- This study underscores the clinical relevance of exo-miRNAs in understanding and managing fibrotic lung diseases.
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