Abstract: Objective To investigate the inhibition of proliferation and regulation of heaptic fibrosis-related genes in HSC-T6 cells by prolyloligopeptidase（POP） inhibitor in vitro. Methods The HSC-T6 cells were cultured,and the POP activity was inhibited by increasing concentrations of POP inhibitor（S17092）. The intracellular level of N-acetyl- seryl-aspartyl-lysyl-proline（Ac-SDKP） was determined by ELISA. The cell apoptosis and cell proliferation were detected by flow cytometry and CCK-8 assay,respectively. The mRNA levels of TGF-β1,α-SMA,monocyte chemoattractant protein 1（MCP-1） and collagen I（Col I） were detected by realtime-PCR,and the POP,TGF-β1,α-SMA, Smad7,p-Smad2/3 and PPAR-γ expression were detected by Western blot. Results The intracellular Ac-SDKP level decreased significantly after co-culture with S17092,the POP inhibitor（P<0.05） as compared to that in the control; the proliferation of HSC-T6 cells was significantly inhibited（P<0.05） and the cell apoptosis was not influenced obviously after S17092 intervention（P>0.05）;the Smad7（P<0.05） and PPAR-γ（P<0.05） protein levels were significantly down-regulated,and the α-SMA protein level was significantly up-regulated（P<0.05） after S17092 intervention;the MCP-1（P<0.05） and α-SMA（P<0.05） mRNA level were significantly up-regulated. Conclusion POP plays a pivotal role in anti-inflammation and anti-fibrosis in HSC cells, which might be related to the regulation of Smad7 and PPAR-γ expression.

Key words: HSC-T6 cells, Prolyloligopeptidase, Transforming growth factor-&#x003b2, -Smad signaling, Peroxisome proliferator activated receptor-&#x003b3, In vitro