Abstract
We investigated the effect of SB525334 (TGF-β receptor type 1 (TβRI) inhibitor) on the epithelial to mesenchymal transition (EMT) signaling pathway in human peritoneal mesothelial cells (HPMCs) and a peritoneal fibrosis mouse model. In vitro experiments were performed using HPMCs. HPMCs were treated with TGF-β1 and/or SB525334. In vivo experiments were conducted with male C57/BL6 mice. The 0.1% chlorhexidine gluconate (CG) was intraperitoneally injected with or without SB52534 administration by oral gavage. Mice were euthanized after 28 days. EMT using TGF-β1-treated HPMCs included morphological changes, cell migration and invasion, EMT markers and collagen synthesis. These pathological changes were reversed by co-treatment with SB525334. CG injection was associated with an increase in peritoneal fibrosis and thickness, which functionally resulted in an increase in the glucose absorption via peritoneum. Co-treatment with SB525334 attenuated these changes. The levels of EMT protein markers and immunohistochemical staining for fibrosis showed similar trends. Immunofluorescence staining for EMT markers showed induction of transformed cells with both epithelial and mesenchymal cell markers, which decreased upon co-treatment with SB525334. SB525334 effectively attenuated the TGF-β1-induced EMT in HPMCs. Cotreatment with SB525334 improved peritoneal thickness and fibrosis and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.
Highlights
Chronic kidney disease (CKD) is an increasingly prominent health problem and can progress to end-stage renal disease, which requires renal replacement therapy
We investigated the effect of SB525334 on the epithelial to mesenchymal transition (EMT) signaling pathway in human peritoneal mesothelial cells (HPMCs) and further examined its influence on the peritoneal membrane in a peritoneal fibrosis (PF)
Trichrome staining showed that the thickness and collagen deposition of the parietal The body weight of mice from D0 to D21 was similar among the three treatment peritoneum in the PF group were increased, but these changes were attenuated by cogroups; it was lower in the PF alone group than in the CTL group at D28 treatment with SB525334 (Figure 4A)
Summary
Chronic kidney disease (CKD) is an increasingly prominent health problem and can progress to end-stage renal disease, which requires renal replacement therapy. Artificial peritoneal dialysate lacks biocompatibility, owing to factors such as high glucose, osmolarity, or glucose degradation products, which results in peritoneal membrane damage [2,3]. Repeated peritoneal membrane damage can lead to fibrosis and/or thickening of the peritoneal membrane. SB525334 is a potent TβRI inhibitor; previous studies have demonstrated that SB525334 blocks TGF-β-induced Smad activation and decreases EMT in some tissues/cell lines [8,9,10,11]. Considering the association between TGF-β signaling and EMT in peritoneal mesothelial cells, SB525334 may attenuate TGF-β signaling, resulting in a decrease in EMT and peritoneal membrane fibrosis. We investigated the effect of SB525334 on the EMT signaling pathway in human peritoneal mesothelial cells (HPMCs) and further examined its influence on the peritoneal membrane in a PF mouse model
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
