title: [Mechanisms of cordycepin on improving renal interstitial fibrosis via regulating eIF2α/TGF-β/Smad signaling pathway].
abstract: OBJECTIVE
  To investigate the effects and mechanisms of cordycepin,an effective component of cordyceps militaris, on renal interstitial fibrosis (RIF) and its related eIF2α/TGF-β/Smad signaling pathway.
  
  
  METHODS
  Firstly, 15 C57BL/6 mice were randomly divided into 3 groups,the control group (Group A), the model group (Group B) and the cordycepin-treated group (Group C). After renal interstitial fibrotic model was successfully established by unilateral ureteral obstruction (UUO), the mice in Group C were intraperitoneally administrated with cordycepin(5 mg x kg(-1) d(-1)) and the ones in Group A and B were administrated with physiological saline for 5 days. At the end of the study, the obstructed kidneys were collected and detected for the pathological changes of RIF, and the mRNA expressions of collagen type I (Col I) and α-smooth muscle actin (α-SMA) in the kidney by Northern blot. Secondly, after renal tubular epithelial (NRK-52E) cells cultured in vitro were exposed to transforming growth factor (TGF) -β with or without cordycepin, the mRNA expressions of Col I and collagen type IV( Col IV) by Northern blot, and the protein expressions of eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α ( p-eIF2α), Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were tested by Western blot.
  
  
  RESULTS
  In vivo, cordycepin alleviated RIF in model mice, including improving fibrotic pathological characteristics and mRNA expressions of Col I and α-SMA. In vitro, cordycepin induced the high expression of p-elF2α, and inhibited the expressions of p-Smad2/3, Col I and Col IV induced by TGF-β in NRK-52E cells.
  
  
  CONCLUSIONS
  Cordycepin attenuates RIF in vivo and in vitro, probably by inducing the phosphorylation of eIF2α, suppressing the expression of p-Smad2/3, a key signaling molecule in TGF-β/Smad signaling pathway, and reducing the expressions of collagens and α-SMA in the kidney.
authors.forename: Liu-bao
authors.initials: LB
authors.lastname: Gu
authors.forename: Rong-wen
authors.initials: RW
authors.lastname: Bian
authors.forename: Yue
authors.initials: Y
authors.lastname: Tu
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Yi-gang
authors.initials: YG
authors.lastname: Wan
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D003839:Deoxyadenosines / Q000494:pharmacology*; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000199:Actins; D003839:Deoxyadenosines; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D017346:Protein Serine-Threonine Kinases; C531557:eIF2alpha kinase, mouse; C058120:cordycepin