Inhibition of FSP۱-MYH۹ 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. FSP۱ (Fibroblast-specific protein ۱) 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 FSP۱ and its interaction with MYH۹ in TGFβ-induced podocyte damage and assess the therapeutic potential of Trifluoperazine (TFP).Methods. Human podocytes were treated with TGF-β, followed by FSP۱ knockdown using siRNA. A series of assays including CCK۸, wound healing, F-actin staining, and CO-IP were performed to assess podocyte injury, migration, and FSP۱-MYH۹ interactions. The effects of TFP on these interactions and podocyte health were also evaluated.Results. TGF-β increased FSP۱ expression in podocytes, leading to cell damage. FSP۱ knockdown reduced injury by improving cell viability and cytoskeletal integrity. CO-IP revealed that FSP۱ interacts with MYH۹ to promote podocyte injury. TFP treatment reduced FSP۱-MYH۹ interaction, alleviating podocyte damage.Conclusion. FSP۱ promotes TGF-β-induced podocyte injury through its interaction with MYH۹, activating the P۳۸ MAPK pathway. TFP disrupts this interaction, offering a promising therapeutic approach for treating podocyte-related kidney diseases.Introduction. Podocytes are crucial for maintaining the glomerular filtration barrier, and their injury is a major contributor to kidney diseases. FSP۱ (Fibroblast-specific protein ۱) 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 FSP۱ and its interaction with MYH۹ in TGFβ-induced podocyte damage and assess the therapeutic potential of Trifluoperazine (TFP).Methods. Human podocytes were treated with TGF-β, followed by FSP۱ knockdown using siRNA. A series of assays including CCK۸, wound healing, F-actin staining, and CO-IP were performed to assess podocyte injury, migration, and FSP۱-MYH۹ interactions. The effects of TFP on these interactions and podocyte health were also evaluated.Results. TGF-β increased FSP۱ expression in podocytes, leading to cell damage. FSP۱ knockdown reduced injury by improving cell viability and cytoskeletal integrity. CO-IP revealed that FSP۱ interacts with MYH۹ to promote podocyte injury. TFP treatment reduced FSP۱-MYH۹ interaction, alleviating podocyte damage.Conclusion. FSP۱ promotes TGF-β-induced podocyte injury through its interaction with MYH۹, activating the P۳۸ MAPK pathway. TFP disrupts this interaction, offering a promising therapeutic approach for treating podocyte-related kidney diseases.

کلیدواژه ها:

FSP۱ ، MYH۹ ، podocyte injury ، trifluoperazine