Role of SIRT1 in the protection of intestinal epithelial barrier under hypoxia and its mechanism
10.3760/cma.j.issn.1671-0274.2014.06.020
- VernacularTitle:沉默信息调节因子1对缺氧条件下肠上皮屏障功能的保护作用及机制
- Author:
Yuanhang MA
1
;
Chao XU
;
Wensheng WANG
;
Ligang SUN
;
Songwei YANG
;
Dingsong LU
;
Yong LIU
;
Hua YANG
Author Information
1. 第三军医大学新桥医院普通外科
- Keywords:
Epithelial barrier function;
Silent information adjusting factor 1;
Transepithelial electrical resistance;
Tight junctions
- From:
Chinese Journal of Gastrointestinal Surgery
2014;(6):602-606
- CountryChina
- Language:Chinese
-
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/cm2, (94±3) Ohm/cm2 and (119±7) Ohm/cm2 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 juncions under hypoxia.
