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Role of MicroRNAs in Respiratory Diseases - An Overview

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MicroRNAs (miRNAs) have a significant role in identifying and managing several respiratory diseases or conditions. Read the article to know more.

Medically reviewed by

Dr. Kaushal Bhavsar

Published At February 9, 2024
Reviewed AtFebruary 28, 2024

Introduction

Chronic respiratory disorders cover a variety of ailments that impact the airways, resulting in progressive impairment of lung function. Several respiratory conditions, such as cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and asthma, collectively impact a significant number of individuals globally.

What Are MicroRNAs?

MicroRNAs (miRNAs) are short, non-coding RNAs that play a significant role in regulating gene expression after transcription.

  • They have been identified as crucial regulators in advancing and developing chronic lung disease.

  • Changes in the number of microRNAs (miRNAs) are observed in lung tissue, inflammatory cells, and blood circulation.

  • These alterations are believed to have dual roles as both causative factors and regulators of disease.

  • The significance of miRNAs in lung pathology has led to the advancement of therapeutic approaches and biomarker technologies based on these molecules.

The pathogenicity and therapeutic potential of miRNAs have been extensively investigated in chronic respiratory disease, characterized by progressive lung function deterioration leading to respiratory insufficiency.

  • The assessment of miRNA expression plays a crucial role in characterizing the functional states of particular tissues.

  • The observed impairment of these miRNAs in various disorders indicates their dynamic involvement in maintaining homeostasis.

What Role Do MicroRNAsPlay in Chronic Respiratory Disease?

  1. Cystic Fibrosis: CF, the most common hereditary disease, is caused by gene mutations. When CFTR's channel malfunctions, it prevents the transfer of chemical compounds such as chloride, sodium, and bicarbonate, resulting in airway dryness and thick mucus discharges, which promotes chronic respiratory infections.

  • Pathogens cannot be adequately eliminated because of large mucus accumulations, resulting in protracted host inflammatory reactions at infection sites. This inflammation produces lung structural changes.

  • Lung injury and tissue remodeling, including epithelium and stroma, can result in airway obstruction in babies as young as one month.

  • Lung disease deteriorates with age and is still the major cause of death.

  • Many miRNAs may help with CF as the miR-16 fixes CFTR's problems with transport by stopping Heat shock protein 90, a binder that helps fold proteins.

  • A microRNA turns off the transforming growth factor beta (TGF-) receptors. TGF- is a protein that helps wounds heal; it is often overproduced in CF lungs and is known to change the intensity of lung disease.

2. Idiopathic Pulmonary Fibrosis: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that is most typically diagnosed in older persons and is characterized by typical interstitial pneumonia and rapid respiratory deterioration.

  • Though the etiology of IPF is unknown, various occupational risk factors are known, including cigarette smoke, farming, and pollution.

  • Airway tissue remodeling caused by excessive extracellular matrix (ECM) protein deposition is involved in disease etiology.

  • These activities are primarily triggered by recurrent damage to the lung epithelium, followed by basement membrane breakdown and activation of myofibroblasts involved in ECM secretion and tissue healing.

  • Myofibroblasts can develop from local and circulating fibroblasts and through the epithelial-to-mesenchymal transition.

  • The unusually rapid development of symptoms and partial reversibility of fibrosis limits the direct clinical application of findings.

  • Several additional miRNAs with anti-fibrotic effects have been identified in IPF models. MicroRNA expression profiling was considerably reduced in IPF lungs, while its activity was inversely linked with fibrosis and fibroblast phenotypic markers.

3. Chronic Obstructive Pulmonary Disease (COPD): Chronic Obstructive Pulmonary Disease (COPD) is characterized by a progressive respiratory obstruction encompassing chronic asthmatic bronchitis and emphysema, with an irreversible nature causing increased mucus production and airway remodeling.

  • Cigarette smoking represents the primary risk factor associated with the development of Chronic Obstructive Pulmonary Disease (COPD), with the likelihood of disease occurrence increasing about both the frequency and duration of smoking.

  • Genetic variables are contributors to the onset and progression of diseases in persons.

  • Smoke inhalation typically irritates the epithelial lining of the lungs, leading to the release of pro-inflammatory cells that initiate both innate and adaptive inflammatory responses.

  • The vulnerability to chronic obstructive pulmonary disease (COPD) may be influenced by factors such as exposure to pollutants, respiratory diseases throughout childhood, and genetic modifiers.

The abundance of global microRNA in alveolar macrophages of cigarette smokers with COPD has been observed to be decreased.

  1. Asthma: It is a chronic respiratory condition characterized by inflammation and narrowing of the airways, prevailing as a very prevalent condition.

  • Asthma is characterized by periodic episodes of inflammation, heightened sensitivity of the airways, swelling of the bronchial tubes, and reversible restriction of airflow.

  • There is a notable diversity in the manifestations of asthma among individuals, resulting in the identification of five distinct subtypes, which are distinguished based on the age at which symptoms first appear, the presence of T helper type 2 cell (TH2) inflammation, the involvement of eosinophilia, the amount of obesity, and whether the asthma attack is triggered by exercise.

  • Asthma development and exacerbation are influenced by hereditary and environmental variables, with disease severity and response presumably being influenced by an interplay between these two elements.

Despite the high incidence of asthma, a limited number of studies have been conducted to investigate the mechanisms of microRNA function in human disease.

What Are the Various Roles of miRNAs?

MicroRNAs (miRNAs) have emerged as promising biomarkers in various research and clinical applications.

  • The investigation of respiratory cells and tissue has significantly advanced the understanding of the role of microRNAs in lung disease.

  • The microRNAs (miRNAs) can persist outside the cell and may be identified in various bodily fluids, including blood, sputum, saliva, and breast milk.

  • These complexes facilitate the uptake of miRNAs by remote cells, enabling them to carry out regulatory roles.

  • The observed variations in miRNA expression patterns across different cell types in chronic lung disorders indicate that analyzing extracellular miRNAs could offer a less invasive method for diagnosing and predicting the progression of these diseases.

  • Examining circulating miRNAs has proven to be highly effective in identifying and characterizing possible biomarkers. The serum samples obtained from persons diagnosed with chronic obstructive pulmonary disease (COPD) and asymptomatic heavy smokers displayed notably elevated levels of miR-21 and decreased levels of miR-181a.

What Are the Therapeutic Use of MicroRNAs (miRNAs)?

  • Innovative treatments targeting miRNAs' function may help solve the underlying causes of respiratory diseases and enhance lung health. MiRNA analogs or anti-miRs can increase miRNA expression or inhibit miRNA activity in disease.

  • The involvement of microRNAs (miRNAs) in disease necessitates the usage of miRNAs by imitating their production or anti-miRs to inhibit miRNA action. As a result, the limits imposed by specialized delivery technologies hinder the development of miRNA therapeutics.

  • The development of therapeutic interventions that specifically target various microRNAs associated with lung disorders. The outcomes of intratracheal siRNA injection trials were diverse due to factors such as mucus, mucociliary clearance pathways, and the complex branching structure of the lungs, which hold back the uptake of siRNA. Nevertheless, several miRNA mimics and anti-miRs have been extensively investigated for their therapeutic potential in the context of other diseases.

Conclusion

Over the past decade, miRNAs have been shown to promote and alleviate chronic respiratory illness. Many of the same miRNAs are involved in numerous respiratory disorders, indicating their importance in maintaining global lung homeostasis and pathways. Thus, miRNAs are considered novel disease biomarkers and therapeutic targets. Several miRNA biology questions must be answered before miRNAs may be used clinically. For low-abundance miRNAs, better tools and tests are needed for high-confidence miRNA assessments. Treatments targeting miRNA are unlikely to work. However, biomarker use is possible. The enormous number of miRNA target genes and diverse cell types involved in each disease have made it difficult to determine their role in disease mechanisms. As new techniques to test and regulate miRNA function are developed, the miRNA control of chronic respiratory disorders will improve, leading to better disease treatment and patient outcomes.

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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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