title: Ginsenoside-Rg1 inhibits endoplasmic reticulum stress-induced apoptosis after unilateral ureteral obstruction in rats.
abstract: OBJECTIVE
  Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are implicated in many fibrotic diseases, including renal fibrosis. Whether Ginsenoside-Rg1 (G-Rg1) could attenuate renal fibrosis via suppression of ER stress and UPR has not been reported. The aim of this study was to explore the effect of G-Rg1 on ER stress and UPR-induced apoptosis in kidneys with unilateral ureteral obstruction (UUO) rat model.
  
  
  METHODS
  Twenty-four male Sprague-Dawley rats were randomly divided into control group, model group and G-Rg1 treatment group. G-Rg1 was administered to rats by intraperitoneal injection. Renal interstitial fibrosis in the model group was developed by UUO in rats. Renal function was estimated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal pathological damage was evaluated by hematoxylin and eosin (HE) and Masson's trichrome staining. The ER stress was assessed with glucose-regulated protein (GRP) 78 expression, and the proapoptotic response was detected with CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 expressions by Western Blot. The number of apoptotic cells was determined by Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) analysis.
  
  
  RESULTS
  UUO for 14 days aggravated renal function, renal damage and renal interstitial fibrosis, activated ER stress response (induction of GRP78 protein), enhanced the proapoptotic response (increase in CHOP and caspase-12 proteins) and increased the number of apoptotic cells (shown by the TUNEL assay). Treatment with G-Rg1 significantly ameliorates the renal pathological lesions and decreases expressions of ER stress-associated proteins and the level of apoptotic cells in kidneys.
  
  
  CONCLUSIONS
  G-Rg1 suppresses renal cell apoptotic and fibrotic process partly through inhibition of ERS- and UPR-related apoptotic pathway in the kidneys after UUO.
authors.affiliation: a The Centre Laboratory , Kunshan First People's Hospital Affiliated to Jiangsu University , Kunshan , China .
authors.forename: Sha-sha
authors.initials: SS
authors.lastname: Li
authors.forename: Jian-ming
authors.initials: JM
authors.lastname: Ye
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Deng
authors.forename: Li-xia
authors.initials: LX
authors.lastname: Yu
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Gu
authors.forename: Qi-feng
authors.initials: QF
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D053454:Caspase 12 / Q000235:genetics; D003404:Creatinine / Q000097:blood; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005355:Fibrosis / Q000188:drug therapy*; D036145:Ginsenosides / Q000008:administration & dosage*; D006360:Heat-Shock Proteins / Q000235:genetics; D020287:In Situ Nick-End Labeling / Q000379:methods; D007668:Kidney / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051742:Transcription Factor CHOP / Q000235:genetics; D014517:Ureteral Obstruction / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053454:Caspase 12; D003404:Creatinine; D036145:Ginsenosides; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat; C035054:ginsenoside Rg1
keywords: Apoptosis; Ginsenoside-Rg1; endoplasmic reticulum stress; renal interstitial fibrosis; unilateral ureteral obstruction