Let-7 Gene Acts as a Guardian of Lung Health, Preventing Pulmonary Fibrosis
A recent study uncovers the vital role of the let-7 gene in protecting the lungs from fibrosis, offering new insights into potential therapies for lung scarring diseases.
Researchers from Baylor College of Medicine and partner institutions have identified the crucial role of the gene let-7 in maintaining lung health and preventing pulmonary fibrosis, a severe and often incurable lung disease characterized by scarring and inflammation. The study, published in Nature Communications, reveals that let-7 functions as a molecular guardian that regulates key pathways involved in lung repair.
Pulmonary fibrosis primarily affects individuals over 50, leading to stiffened lungs that hinder breathing. The disease results from dysfunctional lung repair mechanisms, especially involving alveolar type II (AT2) stem cells responsible for lung regeneration. When these cells malfunction, they produce scar tissue instead of healthy tissue, culminating in fibrosis.
In experiments involving mice, the absence of let-7 caused spontaneous development of lung fibrosis, highlighting its protective role. The research team uncovered that let-7 suppresses genes linked to cancer and fibrotic processes, preventing the inappropriate reprogramming of AT2 cells that promotes scarring. Interestingly, let-7 also modulates epigenetic pathways, influencing histone and DNA modifications associated with cell growth and transformation.
The downregulation of let-7 in human pulmonary fibrosis suggests it could be a potential target for new therapeutic approaches. While the study focused on lung tissue, similar mechanisms might exist in other organs prone to fibrosis, including the liver, kidneys, and heart.
"Our findings open up possibilities for developing treatments that restore let-7 function or mimic its activity, potentially halting or reversing fibrosis," said Dr. Antony Rodríguez. This discovery offers new hope for managing a disease that currently has limited treatment options.
More information:
Matthew J. Seasock et al, Let-7 restrains an epigenetic circuit in AT2 cells to prevent fibrogenic intermediates in pulmonary fibrosis, Nature Communications (2025). DOI: 10.1038/s41467-025-59641-1
Source: medicalxpress.com
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