Abstract
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.
Original language | English (US) |
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Pages (from-to) | 82-94 |
Number of pages | 13 |
Journal | Biological Trace Element Research |
Volume | 140 |
Issue number | 1 |
DOIs | |
State | Published - Apr 2011 |
Keywords
- Apoptosis
- Fibrosis
- Selenium
- TGFbeta1
- Vitamin E
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Clinical Biochemistry
- Inorganic Chemistry
- Biochemistry, medical