Page 35 - JCTR-11-2

Journal of Clinical and
Translational Research miRNA in pneumonia and pulmonary fibrosis

1. Introduction triggered by environmental exposures, such as asbestos, silica,
and ionizing radiation, as well as by connective tissue disorders
Diagnosing childhood pneumonia is difficult due to the and specific drugs. IPF’s root etiology, however, remains
absence of a universally accepted definition. The term largely unknown. A number of lung insults – including
6
“pneumonia” typically denotes a lower respiratory tract toxic, autoimmune, drug-induced, viral, or traumatic
infection (LRTI) characterized by fever, respiratory damage – can lead to pulmonary fibrosis. It represents an
manifestations, and clinical or radiological evidence of exaggerated tissue response to injury. Host response factors
parenchymal engagement. Pathologically, it signifies lung such as age, genetic susceptibility, and environmental factors
inflammation involving various structures such as the may influence disease development. MicroRNAs (miRNAs)
7
airways, alveoli, connective tissues, visceral pleura, and are tiny RNA molecules that do not code for proteins,
vasculature. Radiographically, pneumonia is identified by though they are crucial in various biological processes and
the presence of infiltrates on chest imaging in children developmental pathways. They are usually about 19 – 25
exhibiting symptoms of an acute respiratory ailment. nucleotides long. miRNA regulates gene expression through
1
Pneumonia is a common condition encountered by post-transcriptional signaling mechanisms, resulting in
emergency and primary care physicians and remains the repression of target genes. Their mechanism of action
a leading cause of illness and death among children in is similar to that of endogenous small interfering RNAs.
8
developing countries. However, new vaccines, antibiotics, miRNAs are isolated from plants, animals, and viruses
and advances in diagnostics and surveillance have reduced through molecular cloning and bioinformatics approaches.
9
mortality rates in developed countries.
Their repressive mechanisms vary. In some cases, miRNA
It is essential to define several frequently used in the induces mRNA cleavage by attaching to complementary
clinical context. “Walking pneumonia” typically refers sequences, particularly in the seed region, and then base-
to school-aged children and young individuals who pairing in the central region. This targeted degradation based
exhibit both radiographic and clinical indications of on RNA hydrolysis results in potent gene silencing. miRNAs
10
pneumonia. However, these individuals experience only are a promising field of research due to their involvement in
mild respiratory symptoms that do not disrupt their daily regulating several allergy disorders. Specific miRNAs have
8
routines. Typically, Mycoplasma pneumoniae is the most been implicated in key pathogenic pathways underlying
commonly associated pathogen with walking pneumonia. allergic inflammation, highlighting their potential as novel
Community-acquired pneumonia (CAP) refers to acute therapeutic targets. Moreover, extensive studies have
11
lung infections acquired outside hospital settings, whereas revealed miRNAs’ dual role in cancer, either by suppressing
hospital-acquired pneumonia develops within 48 h of tumor suppressor genes or by modulating oncogenes.
11
hospital admission. The latter also includes pneumonia The intricate nature of miRNA-mediated gene expression
in residents of long-term care homes and those who have regulation is also crucial for neuronal development, function,
recently undergone surgery. Although not exclusive to and survival. Most miRNA genes are transcribed by RNA
older children, the incidence of pneumonia increases polymerase II, forming a long primary transcript, known as
between the ages of 5 and 20 years. Most cases occur in pri-miRNA, which adopts a hairpin structure. Many are
12
2,3
isolation, but further investigation reveals that other family encoded within introns of protein-coding genes, though
members suffer from the same disease and symptoms others exist as independent units or within long non-coding
appear 1 – 3 weeks apart, consistent with the typical RNAs. 12,13 Recent findings suggest that miRNAs act as direct
incubation period. Legionella pneumophila is considered regulators of immune processes contributing to fibrosis.
the most virulent strain, causing rapid and severe illness. Beyond mRNA regulation, certain miRNAs exhibit cytokine-
The incubation period generally ranges from 4 to 6 days like behavior and are referred to as “mirokines” due to their
but may extend up to 28 days. Transmission typically immunomodulatory functions. 14
occurs through inhalation of infectious aerosol generated In this review, we summarize the current understanding
from water mist sources. 4 of the potential pharmacotherapeutic role of miRNAs
Idiopathic pulmonary fibrosis (IPF), a common type of in preventing fibrosis, particularly in the context of
interstitial lung disease, is a chronic, progressive, and usually pneumonia and pulmonary fibrosis. We discuss the
fatal condition, with a median survival of only 3 – 5 years. molecular mechanisms by which miRNAs modulate
In the United States, no treatment has been conclusively the genes and lung homeostasis, highlight miRNAs with
proven effective; however, pirfenidone has been approved demonstrated antifibrotic effect, and address the challenges
for use in Europe, Canada, and Japan. IPF is most common in developing miRNA-based therapies, including delivery
5
in middle-aged and older males, with a prevalence of 14 strategies and off-target effects. A deeper understanding
– 42.7 cases/100,000 people. Pulmonary fibrosis may be of these molecular mechanisms may help medical

Volume 11 Issue 2 (2025) 29 doi: 10.36922/JCTR025080009