목적: Rho GTPases (RhoA, Rac1, and Cdc42) are key regulators of cytoskeletal dynamics and epithelial-to-mesenchymal transition (EMT), processes crucial for tissue remodeling in various diseases. This study aimed to investigate the role of Rho GTPase signaling in chronic rhinosinusitis with nasal polyps (CRSwNP) including EMT, inflammation, and polypogenesis and to assess the therapeutic potential of Rho GTPase inhibition. 방법:Sinonasal tissues were collected from patients with CRSwNP and controls. EMT was induced in primary human nasal epithelial cells (hNECs) using TGF-β1. Rho GTPase inhibitors (EHop-016, ML141, Rhosin, and NSC 23766) were applied to disturb actomyosin metabolism on EMT induction and inflammation through immunofluorescence, western blot, and RT-PCR. siRNA knockdown of RhoA, Rac1, and Cdc42 was performed to further elucidate their role in EMT. An ovalbumin/staphylococcal enterotoxin B (OVA/SEB) murine NP model was treated with EHop-016 to evaluate its effects on polyp formation, EMT, inflammation, and cytokine profiles 결과:Rho GTPase inhibition by EHop-016 significantly suppressed TGF-β1- induced EMT by restoring epithelial markers (E-cadherin) and reducing mesenchymal markers (vimentin and α-SMA) in hNECs. EHop-016 effectively reduced actin polymerization in filopodia and stress fiber development, and Rho GTPase activity (CDC42, RAC1, RhoA, and pRAC1/CDC42). Direct inhibition of actomyosin also suppressed EMT, supporting the critical role of cytoskeletal dynamics in EMT process. siRNA knockdown of RhoA, Rac1, and Cdc42 showed similar effects, confirming that Rho GTPase-mediated cytoskeletal rearrangement is a crucial process in EMT. In the NP murine model, EHop-016 reduced polypoid lesions, restored E-cadherin, and decreased vimentin and α- SMA. Additionally, EHop-016 mitigated neutrophilic and eosinophilic infiltration and reduced pro-inflammatory cytokine levels (IL-4, IL-5, IL-6, IL-10, and IL-17). 결론:Rho GTPase signaling plays a pivotal role in EMT and tissue remodeling in CRSwNP. Inhibition of Rho GTPases effectively suppresses EMT, inflammation, and polyp formation via actin cytoskeletal reorganization. These findings highlight Rho GTPase inhibition as a potential therapeutic strategy for CRSwNP management.