The combination of selenium and vitamin E inhibits type I collagen formation in cultured hepatic stellate cells

Biol Trace Elem Res. 2011 Apr;140(1):82-94. doi: 10.1007/s12011-010-8672-7. Epub 2010 Mar 25.

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 α(1)(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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Collagen Type I / antagonists & inhibitors
  • Collagen Type I / biosynthesis*
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / drug effects*
  • Hepatic Stellate Cells / metabolism*
  • Humans
  • Procollagen / antagonists & inhibitors
  • Procollagen / biosynthesis
  • Sodium Selenite / pharmacology*
  • Structure-Activity Relationship
  • Vitamin E / pharmacology*

Substances

  • Collagen Type I
  • Procollagen
  • Vitamin E
  • Sodium Selenite