The regulation of α 5β 1 integrin expression in human muscle cells

Abstract

The expression of alpha 5 beta 1 integrin was examined in either cloned or fluorescence-activated cell-sorted satellite cells derived from human biceps muscle. Removal of serum and factors required for muscle cell growth and proliferation both induced terminal differentiation and resulted in a coordinate downregulation of mRNA transcripts encoding alpha 5 and beta 1 integrin subunits. A corresponding downregulation of the alpha 5 subunit occurred at the protein level. Treatment of cultures with 5-bromo-2'-deoxyuridine (BUdR), a thymidine analog which inhibits muscle cell differentiation, resulted in increased expression of alpha 5 integrin subunit at both the mRNA and protein levels. However, levels of alpha 5 subunit message and protein were still markedly downregulated on removal of serum and growth factors from BUdR-treated cultures, indicating that downregulation of alpha 5 beta 1 integrin during myogenesis does not require and is not a consequence of muscle cell terminal differentiation. Downregulation of alpha 5 integrin subunit expression could be prevented by maintenance of cells in medium supplemented with serum and growth factors, although no single defined component of this medium could on its own prevent the downregulation of alpha 5 integrin subunit expression. Collectively, these results suggest that downregulation of alpha 5 beta 1 integrin expression is not a consequence of muscle cell terminal differentiation, but is dependent on a combination of exogenous growth factors which are also required for muscle cell growth and proliferation.