PPAR-γ agonists in polycystic kidney disease with frequent development of cardiovascular disorders

Area of Science:

• Nephrology
• Genetics
• Pharmacology

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are genetic disorders characterized by cyst formation in kidneys and other organs.
• These conditions lead to progressive nephron loss, fibrosis, and complications like vascular abnormalities and cardiac defects.
• Aberrant cell proliferation and fluid secretion drive cyst enlargement in polycystic kidney diseases (PKD).

Purpose of the Study:

• To review the therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists in managing PKD.
• To explore how PPAR-γ agonists impact renal, hepatic, and cardiac manifestations of PKD.
• To discuss the underlying signaling pathways affected by PPAR-γ agonists in PKD models.

Main Methods:

• Literature review of studies investigating PPAR-γ agonists in animal models of PKD.
• Analysis of PPAR-γ's role in cell proliferation, fibrosis, and inflammation relevant to PKD.
• Examination of signaling pathways modulated by PPAR-γ agonists, including β-catenin, c-Myc, and TGF-β.

Main Results:

• PPAR-γ agonists have demonstrated efficacy in ameliorating polycystic kidney, liver, and cardiac defects in animal models of PKD.
• These effects are mediated through the modulation of critical signaling pathways such as β-catenin, c-Myc, CFTR, MCP-1, S6, ERK, and TGF-β.
• PPAR-γ's role in regulating cell proliferation, fibrosis, and inflammation is central to its therapeutic action.

Conclusions:

• PPAR-γ agonists represent a potential therapeutic strategy for progressive polycystic kidney diseases (PKD).
• Targeting PPAR-γ may offer a unified approach to address the multi-organ manifestations of PKD, including renal, hepatic, and cardiac complications.
• Further research into PPAR-γ agonists could lead to novel treatments for patients with PKD.