title: Spirolactone provides protection from renal fibrosis by inhibiting the endothelial-mesenchymal transition in isoprenaline-induced heart failure in rats.
abstract: BACKGROUND
  Fibrosis results in excessive accumulation of extracellular matrix proteins, collagen component alteration, and abnormalities in structure and is partly derived from a process called the endothelial-mesenchymal transition involving transforming growth factor β (TGF-β). We investigated whether spironolactone, an aldosterone receptor blocker, attenuated isoprenaline (Iso)-induced heart failure in rats and also studied the mechanism for the same.
  
  
  METHODS
  Sprague-Dawley rats were subcutaneously injected with Iso to induce heart failure, which promoted renal fibrosis; rats with spironolactone treatment were given a gavage of spironolactone (30 or 60 mg/kg/d, for 21 days). Cardiac function and fibrosis indices were measured. Pathological alterations and expression of Type I and III collagen, α-smooth muscle actin, cluster of differentiation-31, and TGF-β were examined.
  
  
  RESULTS
  In Iso-induced heart failure in rats, spironolactone significantly improved cardiac function and decreased myocardial fibrosis, reduced collagen fibrous proliferation in kidney, reduced expression of Type I and III collagen, increased the expression of cluster of differentiation-31, and decreased the expression of α-smooth muscle actin and TGF-β.
  
  
  CONCLUSIONS
  Spironolactone may prevent renal fibrosis by inhibiting the endothelial-mesenchymal transition.
authors.affiliation: Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xi
authors.affiliation: Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jichen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy*; D007674:Kidney Diseases / Q000473:pathology*; D051381:Rats; D013148:Spironolactone / Q000737:chemistry / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013148:Spironolactone
keywords: endothelial-mesenchymal transition; heart failure; renal fibrosis; spironolactone