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

Curr Mol Pharmacol. 2012 Jun;5(2):292-300. doi: 10.2174/1874467211205020292.

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 ligand-dependent 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / etiology*
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Liver Diseases / drug therapy
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Pioglitazone
  • Polycystic Kidney Diseases / complications*
  • Polycystic Kidney Diseases / drug therapy
  • Polycystic Kidney Diseases / pathology
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use

Substances

  • Hypoglycemic Agents
  • PPAR gamma
  • Thiazolidinediones
  • Pioglitazone