Selenium deficiency and thyroid fibrosis. A key role for macrophages and transforming growth factor beta (TGF-beta).
Free radical damage and fibrosis caused by selenium deficiency are thought to be involved in the pathogenesis of myxoedematous cretinism. So far, no pathway explains the link between selenium deficiency and tissue fibrosis. Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids. Necrosis is much increased if the glands are also selenium-deficient, which then evolve to fibrosis. This rat model was reproduced to explore the role of selenium deficiency in defective tissue repair. At first, proliferation indexes of epithelial cells and fibroblasts were comparable between selenium-deficient and control groups. Then, in selenium-deficient thyroids the inflammatory reaction was more marked being mainly composed of macrophages. The proliferation index of the epithelial cells decreased, while that of the fibroblasts increased. These thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the proliferation indexes, and blocked the evolution to fibrosis. In selenium deficiency, an active fibrotic process occurs in the thyroid, in which the inflammatory reaction and an excess of TGF-beta play a key role.
Contempre
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B
Institute of Interdisciplinary Research (IRIBHN), Free University of Brussels, Medicine Faculty, Belgium. bcontemp@med.ulb.ac.be
Le Moine
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O
Dumont
J E
JE
Denef
J F
JF
Many
M C
MC
D000818:Animals; D002455:Cell Division; D004847:Epithelial Cells; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005355:Fibrosis; D006042:Goiter / Q000139:chemically induced; D007249:Inflammation; D008264:Macrophages / Q000737:chemistry / Q000502:physiology*; D010472:Perchlorates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000172:deficiency*; D017670:Sodium Compounds / Q000494:pharmacology; D012974:Sodium Iodide / Q000494:pharmacology; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000502:physiology*
D010472:Perchlorates; D017670:Sodium Compounds; D016212:Transforming Growth Factor beta; C031068:sodium perchlorate; D012974:Sodium Iodide; D012643:Selenium