Objective       To clarify the expression change and significance of phosphofurin acidic cluster sorting protein-2 (PACS-2) in non-alcoholic fatty liver disease (NAFLD).       Methods       An in vitro NAFLD model was established by inducing the steatosis of HepG2 cells using palmitic acid. The cells were collected at the time points of 0

4

8

12

and 24 h after induction. The steatosis levels were measured by oil red staining. Rat NAFLD model was established in SD rats by feeding high fat diet

while the rats fed with normal food were set as control group. These rats were killed at 4

8

12

16 and 20 weeks after feeding. The expression of PACS-2

endoplasmic reticulum stress marker-glucose regulating protein 78 (GRP78)

Bax and Caspase-3 in the cell model and liver tissue samples were detected by q-PCR and Western blotting.       Results      The steatosis of HepG2 cells was induced by fatty acid successfully. The rat NAFLD model was established in SD rats successfully. The relative expression of PACS-2 at mRNA level was significantly decreased in the early stages (4 and 8 h)

but increased in the late stages (12 and 24 h after treatment). That of GRP78 was up-regulated in 8 h

and then reached the highest level in 24 h after induction (P0.01). That of Bax and Caspase-3 was also significantly increased in 12 and 24 h (P0.01). The expression of these proteins showed similar trends as those at mRNA level (P0.01). In the rat NAFLD model

the expression of PACS-2 protein was significantly decreased in the early stages (4 and 8 weeks)

but then up-regulated in the late stages (16 and 20 weeks

P0.01). The expression of GRP78 was up-regulated in 4 weeks

and reached the summit in 20 weeks (P0.01). The expression of Bax and Caspase-3 were significantly up-regulated as compared the control in the late stage of NAFLD(P0.01).       Conclusion      Mild expression of PACS-2 in the early stage of NAFLD might be involved in endoplasmic reticulum stress during the NAFLD process

and its up-regulation in the late stage may be associated with the apoptosis induced hepatocyte injury.