Acute iodine deficiency induces a transient VEGF dependent microvascular response in mammary glands involving HIF-1, ROS and mTOR

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Institutes & Expert groups

  • UCL - Université catholique de Louvain
  • CHR - Centre Hospitalier Régional Mons-Hainaut

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Abstract

Iodine deficiency (ID), which affects almost two billion people worldwide, is associated with breast pathologies such as fibrosis in human and induces breast atypia in animal models. Because ID induces vascular activation in the thyroid, another iodide-uptaking organ, and as breast is also sensitive to ID, we aimed to characterize ID-induced effects on the breast microvasculature in vivo and in two different breast cell lines in vitro. Virgin and lactating NMRI mice received an iodide-deficient diet and a Na+/I- symporter inhibitor for one to 20 days. Some virgin mice were treated with vascular endothelial growth factor A (VEGF) or VEGF receptors inhibitors. In vitro, ID was induced in MCF7 and MCF12A cells by replacing the iodide containing medium by an iodide-deficient medium. In vivo, VEGF expression was increased following ID in mammary tissues. Consequently, ID induced a transient increase in mammary gland blood flow, measured after anesthesia, in virgin and lactating mice, which was repressed by VEGF or VEGF receptor inhibitors. In MCF7 cells, ID induced a transient increase in reactive oxygen species (ROS), followed by an increase in hypoxia-inducible factor-1 (HIF-1) protein and VEGF mRNA expression. Antioxidant N-acetylcysteine and mammalian target of rapamycin (mTOR) inhibitor blocked ID-induced HIF-1 protein increase and VEGF transcription. However, mTOR activity was not inhibited by N-acetylcysteine. Similar responses were observed in MCF12A cells. These data indicate that ID activates the canonical VEGF pathway and mTOR in breast tissues, which provides new insights to better understand the correlation between ID, vascular activation and breast pathologies.

Details

Original languageEnglish
Pages (from-to)C544-C557
JournalAmerican Journal of Physiology Cell Physiology
Volume315
Issue number4
DOIs
Publication statusPublished - 18 Jul 2018

Keywords

  • Breast epithelial cells, mammalian target of rapamycin (mTOR), reactive oxygen species (ROS), vascular endothelial growth factor (VEGF), iodine deficiency

ID: 4339974