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Updated: Mar 11, 2026

Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Plasma microRNAs are associated with acute exacerbation in idiopathic pulmonary fibrosis
Haiyan Min1,2, Shanshan Fan2, Shiyu Song2
1Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.
Background:
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has high short-term mortality with unknown causes. To predict this malignant condition in clinics is challenging. In this study, we aim to demonstrate whether there are miRNAs that differ between AE-IPF and stable IPF, which may be served as reliable biomarker for AE-IPF prediction.
Methods:
Human fibrotic-associated miRNAs arrays were designed to detect miRNAs expression in plasma of 3 AE-IPF patients, 3 Stable-IPF (S-IPF) patients and 3 normal controls (NC). Differentially expressed miRNAs between AE-IPF and S-IPF patients were selected for further analyses. The validation studies were carried out in plasma of 12 AE-IPF patients, 45 S-IPF patients and 51 healthy control subjects. Signaling pathways and cellular processes interacted with validated miRNAs were predicted by DIANA-miRPath.
Results:
According to the array analysis, 6 miRNAs showed differentiated expression between AE-IPF and S-IPF patients (P < 0.05). In the validation studies, let-7d-5p was decreased in S-IPF and further decreased in AE-IPF, when compared to NC (0.0003 ± 0.0002 vs 0.003 ± 0.002, P < 0.01 and 0.0007 ± 0.0005 vs 0.003 ± 0.002, P < 0.01). While miR-25-3p was obviously decreased in S-IPF (0.0002 ± 0.0001 vs 0.0003 ± 0.0003, P < 0.01) but significantly increased in AE-IP (0.0023 ± 0.002 vs 0.0003 ± 0.0003, P < 0.01). In receiver-operator characteristic (ROC) curve analysis, the areas under the curve (AUCs) of miR-25-3p and let-7d-5p were 0.83 and 0.75, respectively. The sensitivity at fixed specificity of 90% was improved from 50% to 66.7% when the two miRNAs were combined. The functional prediction of miRNAs suggested that the loss of anti-fibrotic capacity and the gain of uncontrolled cell growth may be required in AE-IPF pathogenesis.
Conclusions:
In conclusion, miR-25-3p and let-7d-5p in plasma were differentially expressed between AE-IPF and S-IPF. A combination of these two miRNAs may be a potential biomarker for AE-IPF from IPF.
Insights
Plasma miR-25-3p and let-7d-5p levels differ between acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and stable IPF. Combining these microRNAs may serve as a potential biomarker for predicting AE-IPF in patients with IPF.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Biomarker Discovery
Background:
- Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication with high mortality and unknown triggers.
- Predicting AE-IPF in clinical settings is challenging, necessitating the identification of reliable predictive biomarkers.
- MicroRNAs (miRNAs) are being investigated for their potential role in disease prediction and progression.
Purpose of the Study:
- To identify specific miRNAs that exhibit differential expression between AE-IPF and stable IPF (S-IPF) patients.
- To evaluate the potential of these differentially expressed miRNAs as predictive biomarkers for AE-IPF.
- To explore the functional implications of identified miRNAs in the pathogenesis of AE-IPF.
Main Methods:
- Plasma samples from patients with AE-IPF, S-IPF, and healthy controls (NC) were analyzed using miRNA arrays.
- Differentially expressed miRNAs between AE-IPF and S-IPF groups were identified and validated in larger cohorts.
- Receiver-operator characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of candidate miRNAs. Pathway analysis was conducted using DIANA-miRPath.
Main Results:
- Six miRNAs showed differential expression between AE-IPF and S-IPF patients.
- let-7d-5p levels were significantly decreased in S-IPF and further decreased in AE-IPF compared to NC.
- miR-25-3p levels were decreased in S-IPF but significantly increased in AE-IPF compared to S-IPF and NC. The combination of miR-25-3p and let-7d-5p showed an area under the curve (AUC) of 0.83 and improved sensitivity to 66.7% at 90% specificity.
Conclusions:
- Plasma miR-25-3p and let-7d-5p exhibit distinct expression patterns in AE-IPF compared to S-IPF.
- A combination of miR-25-3p and let-7d-5p holds potential as a predictive biomarker for distinguishing AE-IPF from S-IPF.
- Functional analysis suggests that altered miRNA expression in AE-IPF may relate to impaired anti-fibrotic capacity and uncontrolled cell growth.
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