title: [Role of SIRT1 in the protection of intestinal epithelial barrier under hypoxia and its mechanism].
abstract: OBJECTIVE
  To observe the effect of SIRT1 on intestinal barrier function of epithelial Caco-2 cells under hypoxia and investigate its mechanism.
  
  
  METHODS
  Caco-2 cells were randomly divided into three groups: normoxia group (Nx), hypoxia group (Hx,1%O2 for 6 h) and hypoxia plus 40 μmol/L Resveratrol (agonist of SIRT1) group (Hx+Res). Transepithelial electrical resistance (TER) was determined. mRNA and protein expressions of SIRT1 and tight junctions (ZO-1, Occludin, Claudin-1) were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.
  
  
  RESULTS
  Both mRNA and protein expressions of SIRT1 were significantly reduced in Hx group as compared with Nx group (0.40±0.02 vs. 0.70±0.07, P=0.001; 0.37±0.03 vs. 0.76±0.03, P=0.001). The mRNA and protein expressions of SIRT1 were significantly increased in Hx+Res group as compared with Hx group(0.50±0.02 vs. 0.40±0.02, P=0.026; 0.54±0.02 vs. 0.37±0.03, P=0.011). The expression levels of ZO-1, Occludin and Claudin-1 in Hx group were lower than those in Nx group (P<0.05), however, pretreatment with Resveratrol could attenuate the decreased expression of above 3 molecules under hypoxia(P<0.05). TERs of Nx group, Hx group and Hx+Res group were (142±7) Ohm/cm(2), (94±3) Ohm/cm(2) and (119±7) Ohm/cm(2) respectively. Compare with the Nx group, the TER of Hx group was significantly decreased(P<0.05). TER of Hx+Res group was significantly increased compare with Hx group, but it was still significantly lower than that in Nx group(P<0.05).
  
  
  CONCLUSIONS
  Expression of SIRT1 is significantly reduced under hypoxia. Activation of SIRT1 can maintain the epithelial barrier function through regulating the expression of tight junctions under hypoxia.
authors: Department of General Surgery, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China. hwbyang@126.com.
authors: Yuanhang
authors: Y
authors: Ma
authors: Chao
authors: C
authors: Xu
authors: Wensheng
authors: W
authors: Wang
authors: Ligang
authors: L
authors: Sun
authors: Songwei
authors: S
authors: Yang
authors: Dingsong
authors: D
authors: Lu
authors: Yong
authors: Y
authors: Liu
authors: Hua
authors: H
authors: Yang
mesh_terms: D018938:Caco-2 Cells; D015687:Cell Hypoxia; D062445:Claudin-1 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D062793:Occludin / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; C568985:OCLN protein, human; D062793:Occludin; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C447939:SIRT1 protein, human; D056564:Sirtuin 1