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• W2883460766 abstract "AIM: To test whether hepatic stellate cells(HSCs) at different activation stages play different roles in acetaminophen(APAP)-induced acute liver injury(ALI).METHODS: HSCs were isolated from mouse liver and cultured in vitro.Morphological changes of initiation HSCs [HSCs(5d)] and perpetuation HSCs [HSCs(p3)] were observed by immunofluorescence and transmission electron microscopy.The protective effects of HSCderived molecules, cell lysates and HSC-conditioned medium(HSC-CM) were tested in vivo by survival and histopathological analyses.Liver injury was determined by measuring aminotransferase levels in the serum and by histologic examination of tissue sections under a light microscope.Additionally, to determine the molecular mediators of the observed protective effects of initiation HSCs, we examined HSC-CM using a highdensity protein array.RESULTS: HSCs(5d) and HSCs(p3) had different morphological and phenotypic traits.HSCs(5d) presented a star-shaped appearance with expressing α-SMA at non-uniform levels between cells.However, HSCs(p3) evolved into myofibroblast-like cells without lipid droplets and expressed a uniform and higher level of α-SMA.HSC-CM(5d), but not HSC-CM(p3), provided a significant survival benefit and showed a dramatic reduction of hepatocellular necrosis and panlobular leukocyte infiltrates in mice exposed to APAP.However, this protective effect was abrogated at higher cell masses, indicating a therapeutic window of effectiveness.Furthermore, the protein array screenrevealed that HSC-CM(5d) was composed of many chemokines and growth factors that correlated with inflammatory inhibition and therapeutic activity.When compared with HSC-CM(p3), higher levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1γ, hepatocyte growth factor, interleukin-10, and matrix metalloproteinase-2, but lower levels of stem cell factor and Fas-Ligand were observed in HSCCM(5d).CONCLUSION: These data indicated that initiation HSCs and perpetuation HSCs were different in morphology and protei" @default.
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• W2883460766 date "2015-01-01" @default.
• W2883460766 modified "2023-09-24" @default.
• W2883460766 title "Early activated hepatic stellate cell-derived molecules reverse acute hepatic injury" @default.
• W2883460766 hasPublicationYear "2015" @default.
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