Page 42 - JCTR-11-2

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

13. Evidence from human and animal research distinguish patients with pulmonary tuberculosis TB from
healthy individuals. However, such comparisons to
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Few agents, including bleomycin, silica, and viral vectors, healthy controls may limit clinical utility, as the observed
are used to simulate the fibrotic processes observed in ex-miRNA changes could reflect general inflammatory
human IPF. Each model has distinct advantages and responses rather than disease-specific alterations.
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limitations, but among them, the bleomycin-induced

model is the most well-characterized and widely utilized Ex-miRNA biomarkers can also distinguish viral and
model in elucidating molecular mechanisms of fibrogenesis bacterial infections, predict sepsis outcomes, and monitor
and aiding in therapy development. This model closely response to treatment. For instance, miR-223, miR-499,
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resembles human IPF, particularly in collagen deposition miR-15a/b, and miR-16 have been associated with sepsis
and myofibroblast differentiation, making it ideal for diagnosis and mortality, though discrepancies between
studying miRNAs in experimental settings. studies exist. miR-122 has consistently emerged as a
biomarker of viral load and therapeutic response in hepatitis
The let-7 miRNA family was one of the first to be 71
discovered and has been well-studied in the context studies, highlighting its clinical relevance. Although results
are promising, variability in study design, miRNA isolation
of metastasis. Specifically, let-7d was found to be methods, profiling platforms, and data standardization
downregulated in IPF lung tissue, and experimental studies
using bleomycin-induced models demonstrated that complicate the interpretation. Standardization of
decreased let-7d expression contributed to the suppression methodology and validation of study findings are essential
of epithelial markers and upregulation of mesenchymal to realize the potential of identified miRNAs as reliable
markers, indicating its role in promoting EMT. miR-21, biomarkers of infection. Furthermore, analysis of miRNAs
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initially identified as an oncogenic miRNA, is significantly in EXOs, which are actively secreted and reflect cell-specific
molecular changes, may improve both the sensitivity and
upregulated in myofibroblasts and epithelial cells around 27
fibrotic lesions, with antisense probes reducing fibrosis specificity of miRNA-based biomarkers.
markers in mouse models. The miR-200 family, known to 15. Conclusion
promote EMT in cancer, is downregulated in IPF, with the
administration of miR-200c reducing fibrosis in mice. Pneumonia and pulmonary fibrosis are two serious
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Similarly, miR-154, a component of highly expressed respiratory diseases that affect millions of people
miRNA cluster in IPF lungs, has been shown to exhibit worldwide. While current treatment options can slow
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profibrotic activity in in vitro assay. Other miRNAs with the progression of these diseases, they often have limited
confirmed involvement in IPF pathogenesis include: miR- efficacy and can cause unwanted side effects. miRNAs are
29 family (exhibits therapeutic potential), miR-29b (gene small non-coding RNAs that modulate gene expression by
transfer prevents fibrosis in mice), miR-375, miR-199-5p attaching to target mRNAs, thereby inhibiting translation
(overexpressed in fibrotic lesions; downregulated in IPF), or promoting degradation. miRNAs exert a crucial role
the miR-17~92 cluster (downregulated in IPF), miR-145, in different biological activities, including cell division,
miR-326, miR-96, miR-30a/d, miR-92, miR-26a, miR-210, differentiation, inflammation, apoptosis, and metabolism.
and miR-98. 51 Accumulating evidence highlights the regulatory role of
miRNAs in inflammation, fibrosis, and immune responses
14. Clinical use of miRNAs in pulmonary in the lungs, making them a potential pharmacotherapeutic
infections target for the management of pneumonia and pulmonary
fibrosis. Several studies have shown that miRNAs can either
Extracellular miRNAs (ex-miRNAs) are promising promote or inhibit fibrosis by targeting key mediators of
biomarkers for infectious diseases because they are the fibrotic process, including TGF-β. In addition, miRNAs
present in body fluids and can be quantified by real- regulate the activation and differentiation of fibroblast and
time PCR, a method already used in clinical practice. 69 myofibroblast, which are the main effector cells of fibrosis.
A comprehensive review of 57 studies investigated
ex-miRNAs in infectious diseases, such as hepatitis B, These findings suggest that miRNAs may serve not only
hepatitis C, HIV, and tuberculosis, using mainly serum as diagnostic and prognostic biomarkers but also as
and plasma samples, though cerebrospinal fluid, saliva, therapeutic targets for pulmonary fibrosis and pneumonia.
and sputum were also explored. Most studies compared Preclinical studies have demonstrated that miRNA-
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the miRNA profiles of infected individuals with healthy based therapies can reduce inflammation, prevent fibrosis
controls to identify disease-specific signatures. For progression, and improve lung function in animal models
instance, Zhang et al. reported that miR-378, miR-483-5p, with pneumonia and pulmonary fibrosis. Furthermore,
miR-22, miR-29c, miR-101, and miR-320b could accurately some miRNAs have already been recognized as potential

Volume 11 Issue 2 (2025) 36 doi: 10.36922/JCTR025080009