Page 37 - JCTR-11-2

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

After the formation of miRNA duplex (miRNA/ Many of these pathogens share distinct structural
miRNA*), the strands separate in an ATP-independent features, such as a rigid surface containing a polysaccharide
manner. The guide strand of miRNA duplexes is capsule and phosphorylcholine (Figure 1). They also
incorporated into the RNA-induced silencing complex exhibit unique biological behaviors, including natural DNA
(RISC) through the Argonaute (Ago2) protein. The RISC transformation and quorum sensing-induced autolysis. The
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assembly consists of Dicer, TRBP, PACT, and usually a classic lung lesion associated with pneumococcal infection is
combination of Ago2 and GW182, which stabilizes Ago2. lobar pneumonia, which typically begins with peribronchial
The PAZ and MID domains of Ago protein promote the inflammation and progresses to full alveolar involvement.
binding of miRNA to RISC, forming the miRISC complex. The pathological progression has been divided into four
The passenger strand (miRNA*) is normally released and overlapping stages: engorgement, red hepatization, gray
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destroyed. The choice of the guide strand is influenced hepatization, and resolution. The engorgement phase is
by the thermodynamic reliability of the 5’ end, which marked by congestion of the alveolar capillaries, secretion
affects AGO binding. Ultimately, miRISC serves as a of serous fluid into the alveolar space (Figure 1), and the

guide to recognize complementary sequences on target existence of pneumococci in this fluid.In the red hepatization
mRNAs, leading to translational repression or mRNA phase, continued vascular leakage leads to the accumulation
degradation. This post-transcriptional gene silencing of erythrocytes and macrophages within the alveoli, giving
involves interactions between Ago2, GW182, cytoplasmic the lung a liver-like appearance. This is followed by gray
poly(A)-binding protein, and deadenylase complexes such hepatization, in which white blood cells infiltrate the lesion,
as PAN2 – PAN3 and CCR4 – NOT, all of which contribute and phagocytosis (opsonization) occurs. Grossly, the lung
to effective miRNA-mediated mRNA silencing. 11 appears gray due to the dissolution of red cells, deposition
of fibrin, and collapse of capillaries. The final resolution
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4. Pathogenesis of pneumonia stage involves the enzymatic breakdown of fibrin and
Acute pneumonia is an inflammatory disorder that clearance of cellular debris, ultimately restoring normal lung
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primarily affects the alveoli – the tiny air sacs of the architecture. The characteristic symptoms of pneumonia
lungs. Pneumonia usually occurs when people at risk include cough with purulent sputum, fever, chills, pleuritic
are exposed to certain microorganisms, such as bacteria chest pain, confusion, headache, dyspnea, or difficulty in
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or viruses, though fungi and parasites can also cause the breathing.
disease. CAP refers to a lung infection with acute infiltrates 5. miRNA in the diagnosis of pneumonia
evident on chest radiographs in patients who have not
been hospitalized or admitted to a long-term care facility Bronchoalveolar lavage fluid (BALF) can be collected by
within the preceding 14 days. In contrast, nosocomial or bronchoscopy-assisted infusion of physiological saline
nosocomial pneumonia (also known as hospital-acquired into the alveoli, followed by aspiration under negative
pneumonia) develops more than 48 h after hospital pressure. This procedure allows for the acquisition of lower
admission and is not latent at the time of admission. respiratory tract cells and fluid for cytological analysis,
Streptococcus pneumoniae is the most commonly identified microbial culture, and genetic diagnostics. A significant
causative agent for CAP and represents a unique disease constituent of BALF is exosomes (EXOs), which have
spectrum among Gram-positive bacteria. This spectrum is emerged as novel intravascular signaling effectors
also characteristic of two Gram-negative microorganisms implicated in a number of lung illnesses. 25
– Haemophilus influenzae and Neisseria meningitidis. Serum miR-483-3p and miR-29c can be employed as
M. pneumoniae causes a significant proportion of atypical biological markers in the diagnosis of severe pneumonia
pneumonia cases and is transmitted by airborne droplets. in children. Blood samples from kids who had M.
Although it can affect any age group, it primarily affects pneumoniae-associated pneumonia showed a lower
young people aged 5 – 20 years. L. pneumophila is concentration of miR-1323 compared to healthy controls.
particularly serious due to its rapid onset and severe clinical Additionally, in whole blood miRNA profiling, the three
course. Pseudomonas aeruginosa rarely causes pulmonary most upregulated miRNAs – hsa-miR-127-3p, hsa-miR-
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disease in healthy individuals, though it is a significant 493-5p, and hsa-miR-409-3p – effectively distinguished
pathogen in immunocompromised hosts, including between healthy individuals and children with adenovirus-
neonates and patients with human immunodeficiency induced pneumonia. Furthermore, miR-146b has been
virus (HIV) infection. Other relevant pathogens include shown to reduce inflammatory injury in pediatric
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Staphylococcus aureus, Chlamydia psittaci, C. pneumoniae, pneumonia by inhibiting the MyD88/NF-κB signaling
Coxiella burnetii, and Pneumocystis carinii, all of which are pathway. miR-181b is both a diagnostic and prognostic
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potential etiological agents of pneumonia. 20 biomarker for severe community-acquired pneumonia.
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Volume 11 Issue 2 (2025) 31 doi: 10.36922/JCTR025080009