From Injection to Fibrosis: Disrupting Pathogenic Lung Remodeling

"Post-viral pulmonary fibrosis results from dysregulated tissue repair following severe viral lung injury, leading to excessive scar tissue (extracellular matrix ECM deposition) that makes the lungs stiff and reduces the ability to exchange oxygen. Currently, there are no approved treatments specifically designed for this condition, and available therapies have limited efficacy. The absence of targeted, evidence-based treatments highlights a significant therapeutic gap and underscores the need for novel, mechanistically driven approaches, such as microRNA-based interventions, to prevent or mitigate fibrosis following respiratory infections. Our preliminary findings suggest that a small molecule called microRNA-193 (miR-193), may play an important role in the development of pulmonary fibrosis. In laboratory experiments, blocking miR-193 in fibroblasts cells reduced the production of fibrosis-related proteins such as collagen. We also identified 59 genes increased in the lungs of patients with severe COVID-19 that are likely regulated by miR-193 and are involved in tissue remodeling and scar formation. We therefore hypothesize that safely inhibiting miR-193 using a targeted nanoparticle delivery system could reduce excessive scar formation in the lungs. **To test this, we will combine: laboratory experiments with specific cells; analysis of human lung and blood samples from patients with COVID-19 ARDS and non-COVID ARDS; investigation of miR-193 regulation in COVID animal models (Level 3) and human samples; and spatial transcriptomics comparing COVID-19 and non-COVID ARDS lung tissue.** If successful, this work will establish miR-193 as an important molecular regulator of pulmonary fibrosis and may represent a potential target for future therapies."