title: The Inhibitory Effect of Eplerenone on Cell Proliferation in the Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction.
abstract: BACKGROUND
  The unilateral ureteral obstruction (UUO) model not only induces renal interstitial fibrosis in the obstructed kidney but also induces injury in the contralateral kidney. We hypothesized that activation of the mineralocorticoid receptor (MR) may induce fibrosis in the early stage of UUO.
  
  
  METHODS
  Thirty male Sprague-Dawley rats weighting 200 ± 10 g were used in this study and randomly divided into 3 groups: a UUO group, a UUO and eplerenone group, and a sham group. The contralateral kidney and plasma were harvested for further study 10 days after surgery.
  
  
  RESULTS
  The level of plasma aldosterone (869.95 ± 55.851 pg/mL) was significantly higher in the UUO group than that in the sham group (478.581 ± 36.186 pg/mL vs. UUO, p < 0.05). The infiltrated inflammatory cells (F4/80) and deposited collagens were increased significantly in the contralateral kidneys in the UUO group compared to those in the sham group, which were decreased by eplerenone. However, proliferating cell nuclear antigen was increased 2.47 times in the UUO group compared to the sham group in the contralateral kidney (p < 0.01), and those changes are attenuated by eplerenone. The expression of SGK-1 protein and mRNA was upregulated in the contralateral kidney in the UUO group, which is suppressed by eplerenone treatment. NF-κB pathway effecters were also changed markedly in the contralateral kidney in the UUO group and partly reversed by eplerenone.
  
  
  CONCLUSIONS
  Aldosterone induces inflammatory cell proliferation via the MR/SGK-1 and NF-κB pathways and eventually leads to fibrosis in the contralateral kidney.
authors.affiliation: Graduate School, Hebei Medical University, Shijiazhang, China.
authors.forename: Cong-Hui
authors.initials: CH
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liang
authors.forename: Xiang-Ting
authors.initials: XT
authors.lastname: Wang
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Ma
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Liu
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: He
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimosawa
authors.forename: Qing-You
authors.initials: QY
authors.lastname: Xu
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000450:Aldosterone / Q000097:blood; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D000077545:Eplerenone; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000187:drug effects; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D014517:Ureteral Obstruction / Q000473:pathology*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000199:Actins; D000450:Aldosterone; D003094:Collagen; D000077545:Eplerenone; D017874:Immediate-Early Proteins; D000451:Mineralocorticoid Receptor Antagonists; D018809:Proliferating Cell Nuclear Antigen; D017346:Protein Serine-Threonine Kinases; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D014409:Tumor Necrosis Factor-alpha; D000099184:Serum-Glucocorticoid Regulated Kinases; C498862:Acta2 protein, rat
keywords: Aldosterone; Contralateral kidney; Fibrosis; Inflammation; Mineralocorticoid receptor; Proliferation