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

Abstract

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 TGF
β-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.