Downregulation of exosomal let-7d and miR-16 in idiopathic pulmonary fibrosis

Donato Lacedonia,Filomena Simone,Lucia Catucci,Piera Soccio,Massimo Conese,Grazia P Palladino,Sante Di Gioia,Giulia Scioscia,Maria P Foschino-Barbaro,Carla M I Quarato,Roberto Rana,Francesco Sollitto

doi:10.1186/s12890-021-01550-2

Abstract

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is a degenerative interstitial lung disease with both a poor prognosis and quality of life once the diagnosis is made. In the last decade many features of the disease have been investigated to better understand the pathological steps that lead to the onset of the disease and, moreover, different types of biomarkers have been tested to find valid diagnostic, prognostic and therapy response predictive ones. In the complexity of IPF, microRNA (miRNAs) biomarker investigation seems to be promising.MethodsWe analysed the expression of five exosomal miRNAs supposed to have a role in the pathogenesis of the disease from serum of a group of IPF patients (n = 61) and we compared it with the expression of the same miRNAs in a group of healthy controls (n = 15).ResultsIn the current study what emerged is let-7d down-regulation and, unexpectedly, miR-16 significant down-regulation. Moreover, through a cross-sectional analysis, a clustering of the expression of miR-16, miR-21 and miR-26a was found.ConclusionsThese findings could help the individuation of previously unknown key players in the pathophysiology of IPF and, most interestingly, more specific targets for the development of effective medications.

Highlights

Idiopathic Pulmonary Fibrosis (IPF) is a degenerative interstitial lung disease with both a poor progno‐ sis and quality of life once the diagnosis is made
Let-7d is prevented from its physiological action of inhibiting HGMA2, an oncogenic driver protein [10] and a direct enhancer of the expression of TGF-β1 [9], well known as the most important factor for epithelial-mesenchymal transition (EMT) of alveolar epithelial cells-type II (AEC-II) and, fibrosis
In this study we have considered the expression of 5 miRNAs (16, 21, 26a, 210, let-7d) associated with IPF [19] in order to find statistical evidence of down- or up-regulation ofsuch above mentioned miRNAs in serum exosome of affected patients versus healthy controls

Summary

Introduction

Idiopathic Pulmonary Fibrosis (IPF) is a degenerative interstitial lung disease with both a poor progno‐ sis and quality of life once the diagnosis is made. In the last decade many features of the disease have been investi‐ gated to better understand the pathological steps that lead to the onset of the disease and, different types of biomarkers have been tested to find valid diagnostic, prognostic and therapy response predictive ones. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive lung degenerative disease of unknown aetiology and represents the most frequent interstitial lung disease (ILD). Other transduction pathways are considered to be involved in the pathogenesis of IPF, such as MNT (MAX network transcriptional repressor) and Smad, suggesting that an up-regulation of these miRNAs, mir and miR-210, may have a pathological role [11, 12]. The same study has shown a direct relationship between the up-regulation of miR-7 and disease severity [18]

Methods

Discussion

Conclusion