[Effect of 17β-estradiol or resveratrol dimer on hypoxia inducible factor-1α in genioglossus myoblasts and its mechanism].

PURPOSE: To investigate the role of 17β-estradiol (E2) and resveratrol dimer (RD) on HIF-1α and the underlying mechanism.

METHODS: Mice genioglossus myoblasts were isolated and cultured, and the estrogen receptor-α (ERα) shRNA lentivirus was used for gene knockdown. Cells in different groups were treated with different agents (E2, or RD, or E2 and LY294002), then incubated in normoxia or hypoxia for 24 h, the expressions of HIF-1α, ERα, ERβ, total-Akt and phospho-Akt were detected using qRT-PCR and Western blot. Statistical analysis was completed with SPSS 17.0 software package.

RESULTS: Both E2 and RD inhibited the overexpression of HIF-1α induced by hypoxia at mRNA and protein levels, and these effects were eliminated by genetic silencing of ERα by RNAi. Mechanically, E2 activated PI3K/Akt pathways to induce HIF-1α expression.

CONCLUSIONS: ERα may be responsible for down-regulation of HIF-1α by E2 or RD via activation of downstream PI3K/Akt pathways.