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Transforming Growth Factor-β Regulates Stearoyl Coenzyme A Desaturase Expression through a Smad Signaling Pathway

2002; Elsevier BV; Volume: 277; Issue: 1 Linguagem: Inglês

10.1074/jbc.m108730200

1083-351X

William Samuel, Chandrasekharam N. Nagineni, R. Krishnan Kutty, W. Tony Parks, Joel S. Gordon, Stephen M. Prouty, John J. Hooks, Barbara Wiggert,

Peroxisome Proliferator-Activated Receptors

The regulation of stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the synthesis of unsaturated fatty acids, is physiologically important because the ratio of saturated to unsaturated fatty acids is thought to control cellular functions by modulating the structural integrity and fluidity of cell membranes. Transforming growth factor-β (TGF-β), a multifunctional cytokine, increased SCD mRNA expression in cultured human retinal pigment epithelial cells. This response was elicited by all three TGF-β isoforms, β1, β2, and β3. However, SCD mRNA expression was not increased either by other members of the TGF-β family or by other growth factors or cytokines. TGF-β also increased SCD mRNA expression in several other cell lines tested. The increase in SCD mRNA expression was preceded by a marked increase in Smad2 phosphorylation in TGF-β-treated human retinal pigment epithelial cells. TGF-β did not induce SCD mRNA expression in a Smad4-deficient cell line. However, Smad4 overexpression restored the TGF-β effect in this cell line. Moreover, TGF-β-induced SCD mRNA expression was effectively blocked by the overexpression of Smad7, an inhibitory Smad. Thus, a TGF-β signal transduction pathway involving Smad proteins appears to regulate the cellular expression of the SCD gene, and this regulation may play an important role in lipid metabolism.