title: Wnt/β-catenin signaling and renin-angiotensin system in chronic kidney disease.
abstract: OBJECTIVE
  Intrarenal activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of hypertension and chronic kidney diseases (CKD). However, how RAS genes are regulated in vivo was poorly understood until recently. This review focuses on recent findings of the transcriptional regulation of RAS components, as well as their implication in developing novel strategies to treat the patients with CKD.
  
  
  RESULTS
  Bioinformatics analyses have uncovered the presence of putative binding sites for T-cell factor/β-catenin in the promoter region of all RAS genes. Both in-vitro and in-vivo studies confirm that Wnt/β-catenin is the master upstream regulator that controls the expression of all RAS components tested, such as angiotensinogen, renin, angiotensin converting enzyme and the angiotensin II type I receptor in the kidney. Targeted inhibition of Wnt/β-catenin, by either small molecule ICG-001 or endogenous Wnt antagonist Klotho, represses RAS activation and ameliorates proteinuria and kidney injury. Blockade of Wnt/β-catenin signaling also normalizes blood pressure in a mouse model of CKD.
  
  
  CONCLUSIONS
  These recent studies identify Wnt/β-catenin as the master regulator that controls multiple RAS genes, and suggest that targeting this upstream signaling could be an effective strategy for the treatment of patients with hypertension and CKD.
authors.affiliation: aState Key Laboratory of Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China bDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: Youhua
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin