Autophagy Induced by HIF1α Overexpression Supports Trophoblast Invasion by Supplying Cellular Energy

Mikiko Yamanaka-Tatematsu, Akitoshi Nakashima, Naonobu Fujita, Tomoko Shima, Tamotsu Yoshimori, Shigeru Saito

    Research output: Contribution to journalArticlepeer-review

    44 Citations (Scopus)

    Abstract

    Extravillous trophoblasts (EVTs) characterize the invasion of the maternal decidua under low oxygen and poor nutrition at the early feto-maternal interface to establish a successful pregnancy. We previously reported that autophagy in EVTs was activated under 2% O2 in vitro, and autophagy activation was also observed in EVTs at the early feto-maternal interface in vivo. Here, we show that autophagy is an energy source for the invasion of EVTs. Cobalt chloride (CoCl2), which induces hypoxia inducible factor 1α (HIF1α) overexpression, activated autophagy in HTR8/SVneo cells, an EVT cell line. The number of invading HTR8-ATG4BC74A cells, an autophagy-deficient EVT cell line, was markedly reduced by 81 percent with the CoCl2 treatment through the suppression of MMP9 level, although CoCl2 did not affect the cellular invasion of HTR8-mStrawberry cells, a control cell line. HTR8-ATG4BC74A cells treated with CoCl2 showed a decrease in cellular adenosine triphosphate (ATP) levels and a compensatory increase in the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2RX7), which is stimulated with ATP, whereas HTR8-mStrawberry cells maintained cellular ATP levels and did not affect P2RX7 expression. Furthermore, the decreased invasiveness of HTR8-ATG4BC74A cells treated with CoCl2 was neutralized by ATP supplementation to the level of HTR8-ATG4BC74A cells treated without CoCl2. These results suggest that autophagy plays a role in maintaining homeostasis by countervailing HIF1α-mediated cellular energy consumption in EVTs.

    Original languageEnglish
    Article numbere76605
    JournalPloS one
    Volume8
    Issue number10
    DOIs
    Publication statusPublished - 2013 Oct 3

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

    Fingerprint Dive into the research topics of 'Autophagy Induced by HIF1α Overexpression Supports Trophoblast Invasion by Supplying Cellular Energy'. Together they form a unique fingerprint.

    Cite this