Fasudil attenuates oxidative stress-induced partial epithelial-mesenchymal transition of tubular epithelial cells in hyperuricemic nephropathy via activating Nrf2

• DOI: 10.1016/j.ejphar.2024.176640
• Publication Date: 2024-05-14T00:12:45Z
• Authors: Yun Cao; Yanni Wang; Weiwei Li; Jianan Feng; Yao Chen; Ruike Chen; Langtao Hu; Jiali Wei
• Keywords: Fasudil; Rho kinase inhibitor

Anti-partial epithelial-mesenchymal transition (pEMT) treatment of renal tubular epithelial cells (TECs) represents a promising therapeutic approach. Hyperuricemia nephropathy (HN) arises as consequence hyperuricemia (HUA)-induced tubulointerstitial fibrosis (TIF). Studies have suggested that the Ras homolog member A (RhoA)/Rho-associated kinase (ROCK) pathway is crucial signaling transduction system in fibrosis. Fasudil, RhoA/ROCK inhibitor, has exhibited potential to prevent progress. However, its impact on pEMT TECs HN remains unclear. Here, an rat model and uric acid (UA)-stimulated human kidney 2 (HK2) cell were established treated with Fasudil explore effects. Furthermore, underlying mechanism action involved attenuation by during was probed using multiple molecular approaches. The significant dysfunction histopathological damage, whereas vitro vivo experiments further confirmed status accompanied activation oxidative stress exposed UA. Notably, ameliorated these pathological changes, this consistent trend ROCK silencing vitro. Mechanistically, we identified Neh2 domain nuclear factor erythroid 2-related (Nrf2) target for first time. targets Nrf2 antagonizes attenuate HN. Our findings suggest attenuates stress-induced targeting activation. Thus, agent