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Am J Physiol Gastrointest Liver Physiol 283: G1051-G1061, 2002; doi:10.1152/ajpgi.00128.2002
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Vol. 283, Issue 5, G1051-G1061, November 2002

DLPC decreases TGF-beta 1-induced collagen mRNA by inhibiting p38 MAPK in hepatic stellate cells

Qi Cao, Ki M. Mak, and Charles S. Lieber

Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center and Mount Sinai School of Medicine, Bronx, New York 10468

Dilinoleoylphosphatidylcholine (DLPC), the active component of polyenylphosphatidylcholine extracted from soybeans, decreases collagen accumulation induced by TGF-beta 1 in cultured hepatic stellate cells (HSCs). Because DLPC exerts antioxidant effects and TGF-beta 1 generates oxidative stress, we evaluated whether the antifibrogenic effect of DLPC is linked to its antioxidant action. In passage 1 culture of rat HSCs, TGF-beta 1 induced a concentration-dependent increase in procollagen-alpha 1(I) mRNA levels and enhanced intracellular H2O2 and superoxide anion formation and lipid peroxidation but decreased GSH levels. These changes were prevented by DLPC. Upregulation of collagen mRNA by TGF-beta 1 was likewise inhibited by catalase and p38 MAPK inhibitor SB-203580, suggesting involvement of H2O2 and p38 MAPK signaling in this process. TGF-beta 1 or addition of H2O2 to HSCs activated p38 MAPK with a rise in procollagen mRNA level; these changes were blocked by catalase and SB-203580 and likewise by DLPC. alpha -Smooth muscle actin abundance in HSCs was not altered by TGF-beta 1 treatment (with or without DLPC), indicating that downregulation of procollagen mRNA by DLPC was not due to alteration in HSC activation. These results demonstrate that DLPC prevents TGF-beta 1-induced increase in collagen mRNA by inhibiting generation of oxidative stress and associated H2O2-dependent p38 MAPK activation, which explains its antifibrogenic effect. DLPC, an innocuous phospholipid, may be considered for prevention and treatment of liver fibrosis.

dilinoleoylphosphatidylcholine; oxidative stress; antioxidant; catalase; p38 inhibitor SB-203580


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