Rapamycin Protects from Type-I Peritoneal Membrane Failure Inhibiting the Angiogenesis, Lymphangiogenesis, and...

Area of Science:

• Nephrology
• Immunology
• Cell Biology

Background:

• Peritoneal dialysis (PD) is crucial for long-term survival but can cause peritoneal membrane (PM) damage.
• Chronic inflammation, fibrosis, angiogenesis, and lymphangiogenesis in the PM are linked to mesothelial-to-mesenchymal transition (MMT) and endothelial-to-mesenchymal transition (Endo-MT).

Purpose of the Study:

• To investigate the potential protective effects of Rapamycin on the peritoneal membrane in PD.
• To evaluate Rapamycin's impact on PM changes, MMT, Endo-MT, and related molecular markers.

Main Methods:

• Mice underwent PD with or without Rapamycin treatment.
• PM thickness, submesothelial vessel density, MMT, and Endo-MT were assessed.
• Peritoneal water transport and effluent levels of VEGF, TGF-β, and TNF-α were measured.
• In vitro studies examined Rapamycin's effect on mesothelial cell VEGF synthesis and release.

Main Results:

• Rapamycin treatment reduced PM thickness and submesothelial blood and lymphatic vessels.
• Decreased MMT and Endo-MT were observed in the Rapamycin group.
• Peritoneal water transport was preserved, and PD effluent levels of VEGF, TGF-β, and TNF-α were lower with Rapamycin.
• In vitro, Rapamycin decreased VEGF synthesis and inhibited VEGF-C and VEGF-D release.

Conclusions:

• Rapamycin demonstrates a protective effect on the peritoneal membrane in PD.
• It exerts antifibrotic and antiproliferative effects on blood and lymphatic vessels.
• Rapamycin inhibits Endo-MT and partially MMT, offering a potential therapeutic strategy for PD patients.