Down-regulation of HSP70 sensitizes gastric epithelial cells to apoptosis and growth retardation triggered by H. pylori.
BACKGROUND
H. pylori infection significantly attenuated the expression of HSP70 in gastric mucosal cells. However, the role of HSP70 cancellation in H. pylori-associated cell damages is largely unclear.


METHODS
Small interfering RNA (siRNA) was used to down-regulate HSP70 in gastric epithelial cell lines AGS. The transfected cells were then incubated with H. pylori and the functions of HSP70 suppression were observed by viability assay, cell cycle analyses and TUNEL assay. HSP70 target apoptotic proteins were further identified by Western blot.


RESULTS
The inhibition of HSP70 has further increased the effect of growth arrest and apoptosis activation triggered by H. pylori in gastric epithelial cells. The anti-proliferation function of HSP70 depletion was at least by up-regulating p21 and cell cycle modulation with S-phase accumulation. An increase of apoptosis-inducing factor (AIF) and cytosolic cytochrome C contributes to the activation of apoptosis following down-regulation of intracellular HSP70. Extracellular HSP70 increased cellular resistance to apoptosis by suppression the release of AIF and cytochrome c from mitochondria, as well as inhibition of p21 expression.


CONCLUSIONS
The inhibition of HSP70 aggravated gastric cellular damages induced by H. pylori. Induction of HSP70 could be a potential therapeutic target for protection gastric mucosa from H. pylori-associated injury.
Gastroenterology laboratory, Clinical Research Institute, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310016 Hangzhou, People's Republic of China.
Weili
W
Liu
Yan
Y
Chen
Gaofeng
G
Lu
Leimin
L
Sun
Jianmin
J
Si
D017209:Apoptosis; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D004847:Epithelial Cells / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction
D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins