Title:PPAR-γ Agonists in Polycystic Kidney Disease with Frequent Development of Cardiovascular Disorders
Volume: 5
Author(s): Shizuko Nagao and Tamio Yamaguchi
Affiliation:
Keywords:
Peroxisome proliferator-activated receptor-γ, cell proliferation, fibrosis, inflammation, polycystic kidney diseases, cardiovascular disorder
Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common of the monogenic disorders and
is characterized by bilateral renal cysts; cysts in other organs including liver, pancreas, spleen, testis and ovary; vascular
abnormalities including intracranial aneurysms and subarachnoid hemorrhage; and cardiac disorders such as left
ventricular hypertrophy (LVH), mitral valve regurgitation, mitral valve prolapse and aortic regurgitation. Autosomal
recessive polycystic kidney disease (ARPKD) is an early-onset multisystem disorder characterized by polycysts divided
from the renal collecting ducts, congenital hepatic fibrosis, and ductal plate malformation complicated by pulmonary
hyperplasia and systemic hypertension. In these polycystic kidney diseases (PKD), progressive enlargement of the cysts
results from the aberrant proliferation of tubule epithelial cells and trans-epithelial fluid secretion leading to extensive
nephron loss and interstitial fibrosis. Peroxisome proliferator-activated receptor-γ (PPAR-γ), a member of the liganddependent
nuclear receptor superfamily, is expressed in a variety of tissues, including kidneys and liver, and plays
important roles in cell proliferation, fibrosis, and inflammation. PPAR-γ agonists ameliorate polycystic kidney, polycystic
liver and cardiac defects through β-catenin, c-Myc, CFTR, MCP-1, S6, ERK, and TGF-β signaling pathways in animal
models of PKD. In this review, we describe the possible therapeutic value of PPAR-γ agonists in the treatment of renal
and hepatic manifestations, and cardiac defects in progressive PKD.
