TY - JOUR
T1 - The combination of selenium and vitamin e inhibits type i collagen formation in cultured hepatic stellate cells
AU - Mezey, Esteban
AU - Liu, Xiaopu
AU - Potter, James J.
N1 - Funding Information:
This work was supported by Grant AA000626 from the United States Public Health Service E.Mezey(*).X.Liu.J.J.Potter Department of Medicine, The Johns Hopkins University School of Medicine, 921 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205-2195, USA e-mail: [email protected]
PY - 2011/4
Y1 - 2011/4
N2 - This study investigated the effects of sodium selenite (Se) and of vitamin E (d-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α1(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.
AB - This study investigated the effects of sodium selenite (Se) and of vitamin E (d-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α1(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.
KW - Apoptosis
KW - Fibrosis
KW - Selenium
KW - TGFbeta1
KW - Vitamin E
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U2 - 10.1007/s12011-010-8672-7
DO - 10.1007/s12011-010-8672-7
M3 - Article
C2 - 20336493
AN - SCOPUS:79952487405
SN - 0163-4984
VL - 140
SP - 82
EP - 94
JO - Biological Trace Element Research
JF - Biological Trace Element Research
IS - 1
ER -