Inhibition of FSP1-MYH9 Interaction Reduces TGF-β-induced Podocyte Injury: Potential Therapeutic Role of Trifluoperazine

Introduction. Podocytes are crucial for maintaining the glomerular filtration barrier, and their injury is a major contributor to kidney diseases. FSP1 (Fibroblast-specific protein 1) has been implicated in various pathological conditions but its role in podocyte injury, especially under TGF-β (Transforming Growth Factor-Beta) stimulation, is not well understood. This study aims to explore the involvement of FSP1 and its interaction with MYH9 in TGFβ-induced podocyte damage and assess the therapeutic potential of Trifluoperazine (TFP).Methods. Human podocytes were treated with TGF-β, followed by FSP1 knockdown using siRNA. A series of assays including CCK8, wound healing, F-actin staining, and CO-IP were performed to assess podocyte injury, migration, and FSP1-MYH9 interactions. The effects of TFP on these interactions and podocyte health were also evaluated.Results. TGF-β increased FSP1 expression in podocytes, leading to cell damage. FSP1 knockdown reduced injury by improving cell viability and cytoskeletal integrity. CO-IP revealed that FSP1 interacts with MYH9 to promote podocyte injury. TFP treatment reduced FSP1-MYH9 interaction, alleviating podocyte damage.Conclusion. FSP1 promotes TGF-β-induced podocyte injury through its interaction with MYH9, activating the P38 MAPK pathway. TFP disrupts this interaction, offering a promising therapeutic approach for treating podocyte-related kidney diseases.