Page 39 - JCTR-11-2

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

pneumonia research reflects their growing importance (n=9). In this study, 11 significantly differentially
in pathogenesis elucidation, disease assessment, and expressed miRNAs were identified: six (including hsa-
therapeutic intervention. 34 miR-34a and hsa-miR-455) were upregulated and five
However, most of these research findings were obtained (including hsa-let-7f-1) were desensitized. These miRs
from laboratory experiments. Only a small subset of retained their expression patterns in control, non-severe,
37

miRNAs have been examined in clinical trials, with nearly and severe pneumonia samples. Analysis of predicted
none of them showing substantial improvement and most differentially expressed miR target genes – such as kalirin
of them still waiting to be approved. Challenges include (KALRN), Ras homolog family member A (RHOA),
low sensitivity and specificity of some miRNA biomarkers, beta-catenin (CTNNB1), RNA polymerase II subunit K
issues related to nucleic acid delivery, in vivo stability, (POLR2K), and amyloid precursor protein (APP) –
cellular uptake, and off-target effects due to hybridization. revealed enrichment in pathways associated with adherens
31
junctions and Wnt signaling. Specifically, hsa-miR-200b
Overcoming these obstacles – such as improving site- was identified to target KALRN, whereas hsa-let-7f-1
specific intracellular transport and reducing adverse
interactions – will be crucial for the widespread use of was predicted to target RHOA, CTNNB1, POLR2K, and
miRNA-based approaches for the therapeutic management APP. Hsa-let-7f-1 was involved in carcinoma and the
of pneumonia. 31 Notch signaling mechanisms, indicating its role in the
development of pneumonia. Conversely, hsa-miR-455
7. miRNAs in bacterial infection was found to suppress pneumonia, while hsa-miR-200b
was found to promote the development of pneumonia by
In recent years, widespread overuse of antibiotics has targeting KALRN. This study identifies potential miRNA
significantly contributed to the emergence of bacterial biomarkers and therapeutic targets for pneumonia
resistance, a problem exacerbated by the stagnation in management. 37
the development of new antibiotics due to outdated
drug discovery methodologies. Thus, serious bacterial 9. Pathogenesis of pulmonary fibrosis
35
infections continue to pose one of the most significant Pulmonary fibrosis represents the terminal stage
challenges to global public health, highlighting the of several diffuse parenchymal lung diseases and is
urgent need for alternative antimicrobial strategies. 36 characterized by extracellular matrix fibrosis, which
Recent studies have extensively explored the roles of ultimately leads to the eradication of normal lung
miRNA in bacterial infections. miRNAs have been found architecture and respiratory insufficiency. 38 A key
to be crucial in post-transcriptional gene regulation, feature of interstitial fibrosis is the deposition of excess
significantly influencing the interactions between host extracellular matrix (ECM) components within lung
cells and bacterial pathogens. By regulating the expression tissues. These include elastic fibers, laminin, fibronectin,
of specific genes, miRNAs can affect the host’s immune and nidogen, with collagens being the most abundant.
activity and the ability of pathogens to evade or counter The most common type of pulmonary fibrosis is IPF,
that response. These results suggest that miRNAs may which is characterized by impaired AECs function and
29
serve as potential targets for novel therapeutic approaches stimulation of wound healing signaling pathway in
and open new avenues for fighting bacterial infections. response to lung tissue injury. Immune responses are
39
Developing miRNA-based therapies could provide a also implicated in the IPF pathogenesis. The uncontrolled
means to circumvent traditional antibiotic resistance cytokines production (Figure 2) contributes to altered
and improve treatment outcomes for bacterial diseases. cellular behavior and immune imbalance, promoting
Therefore, further research into the role of miRNAs in a profibrotic microenvironment. The pathogenesis
40
bacterial infections is essential for the development of begins with endothelial and epithelial injuries, triggering
these innovative antibacterial strategies. 31
inflammation and edema. Chemical mediators enter the
8. RNA-sequencing and bioinformatics interstitium of the infected regions, activating fibroblasts.
analysis This causes the cells to migrate, proliferate, or generate
excess collagen. In patients with pulmonary fibrosis,
39
Recent research has increasingly focused on identifying interleukin concentration in blood, lung tissue, and/or
miRNA biomarkers to facilitate the development of BLF are affected. Interleukin level changes also occur
targeted therapy for pneumonia. In an effort to uncover between different stages of pulmonary fibrosis. These
such biomarkers, RNA was extracted from plasma samples changes in interleukin concentration may reflect and
of patients classified into three groups: Severe pneumonia influence the inflammatory state and are also useful for
(n=9), non-severe pneumonia (n=9), and healthy control evaluating disease progression and severity. 40

Volume 11 Issue 2 (2025) 33 doi: 10.36922/JCTR025080009