Microvascular activation by iodine deficiency and X-radiation in non-thyroidal NIS-expressing organs

Research output: ThesisDoctoral thesis

Authors

  • Jessica Vanderstraeten

Institutes & Expert groups

  • UCL - Université catholique de Louvain

Documents & links

Abstract

Iodine is an essential element required for diverse physiological functions, including thyroid hormone production. Beside thyroid, other organs take up iodide via the sodium/iodide symporter (NIS), such as stomach and salivary and mammary glands. Beside its secretion into milk, iodide has been suggested to offer an antioxidant protection in the three mentioned tissues, along with a recycling role via salivary glands and stomach secretion of iodide into their respective fluids to avoid kidney clearance. Several studies have linked iodine deficiency (ID), which is still a global problem, to functional alterations and pathologies of those organs. In thyroid, ID is known to activate a TSH-independent microvascular response. We have thus hypothesized that those organs could also activate a vascular response when facing ID. In this work, we show that acute ID increases vascular endothelial factor (VEGF) expression in salivary glands, stomach, and lactating and virgin mammary glands, transiently leading to increased blood perfusion in salivary and mammary glands. This VEGF up-regulation was shown to depend on non-mitochondrial ROS and the mechanistic target of rapamycin (mTOR) in two breast cell lines: MCF7 and MCF12A. Because X-rays are able to activate angiogenic processes, we hypothesized that they could further increase ID-induced response. The combined exposure to ID and to 3 Gy of X-rays indeed led to additive effects on ROS production and VEGF mRNA expression, but in MCF12A cells only. Our results suggest that ROS induced by radiations with or without iodide come at least partly from mitochondria in this cell line. In conclusion, ID induces a transient microvascular response in all three organs studied as it does in thyroid. This microvascular response might be a common reaction of NIS-expressing organs to try to improve iodide supply, but, in the case of stomach and salivary glands, might also be a mechanism to increase iodide recycling and spare it for thyroid. The increase in VEGF expression, along with mTOR activation and ROS formation in breast, could also provide new insight in the research on the link between ID and NIS-expressing organs pathologies. Furthermore, as radiations increase ID-induced oxidative stress and VEGF mRNA up-regulation in one of the two breast cell lines studied, iodide intake should not be overlooked in radiation prevention policies.

Details

Original languageEnglish
Awarding Institution
  • UCL - Université catholique de Louvain
Supervisors/Advisors
  • Derradji, Hanane, Supervisor
  • Gérard, Anne-Catherine, Supervisor, External person
  • Many, Marie-Christine, Supervisor, External person
Publisher
  • UCL - Université Catholique de Louvain
Publication statusPublished - 13 Mar 2018

Keywords

  • radiation, microvascular , salivary, mamary, deficiency, Iodine

ID: 4339931