[PMID]: | 28911146 |
[Au] Autor: | van Gucht ALM; Meima ME; Moran C; Agostini M; Tylki-Szymanska A; Krajewska MW; Chrzanowska K; Efthymiadou A; Chrysis D; Demir K; Visser WE; Visser TJ; Chatterjee K; van Dijk TB; Peeters RP |
[Ad] Endereço: | Department of Internal Medicine, Erasmus University Medical Center, 3000 Rotterdam, The Netherlands. |
[Ti] Título: | Anemia in Patients With Resistance to Thyroid Hormone α: A Role for Thyroid Hormone Receptor α in Human Erythropoiesis. |
[So] Source: | J Clin Endocrinol Metab;102(9):3517-3525, 2017 Sep 01. |
[Is] ISSN: | 1945-7197 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Context: Patients with resistance to thyroid hormone (TH) α (RTHα) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTHα patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)α in erythropoiesis. Objective: To investigate whether a defect in TRα affects the maturation of red blood cells in RTHα patients. Design, Setting, and Patients: Cultures of primary human erythroid progenitor cells (HEPs), from peripheral blood of RTHα patients (n = 11) harboring different inactivating mutations in TRα (P398R, F397fs406X, C392X, R384H, A382fs388X, A263V, A263S), were compared with healthy controls (n = 11). During differentiation, erythroid cells become smaller, accumulate hemoglobin, and express different cell surface markers. We assessed cell number and cell size, and used cell staining and fluorescence-activated cell sorter analysis to monitor maturation at different time points. Results: After ∼14 days of ex vivo expansion, both control and patient-derived progenitors differentiated spontaneously. However, RTHα-derived cells differentiated more slowly. During spontaneous differentiation, RTHα-derived HEPs were larger, more positive for c-Kit (a proliferation marker), and less positive for glycophorin A (a differentiation marker). The degree of abnormal spontaneous maturation of RTHα-derived progenitors did not correlate with severity of underlying TRα defect. Both control and RTHα-derived progenitors responded similarly when differentiation was induced. T3 exposure accelerated differentiation of both control- and RTHα patient-derived HEPs. Conclusions: Inactivating mutations in human TRα affect the balance between proliferation and differentiation of progenitor cells during erythropoiesis, which may contribute to the mild anemia seen in most RTHα patients. |
[Mh] Termos MeSH primário: |
Anemia/genética Eritropoese/genética Regulação da Expressão Gênica Receptores alfa dos Hormônios Tireóideos/genética Síndrome da Resistência aos Hormônios Tireóideos/genética
|
[Mh] Termos MeSH secundário: |
Adolescente Adulto Anemia/epidemiologia Anemia/fisiopatologia Estudos de Casos e Controles Células Cultivadas Criança Pré-Escolar Eritrócitos/metabolismo Feminino Seres Humanos Incidência Masculino Meia-Idade Mutação Prognóstico Valores de Referência Papel (Figurativo) Células-Tronco/citologia Células-Tronco/fisiologia Síndrome da Resistência aos Hormônios Tireóideos/epidemiologia Síndrome da Resistência aos Hormônios Tireóideos/fisiopatologia Adulto Jovem
|
[Pt] Tipo de publicação: | COMPARATIVE STUDY; JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Thyroid Hormone Receptors alpha) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171012 |
[Lr] Data última revisão:
| 171012 |
[Sb] Subgrupo de revista: | AIM; IM |
[Da] Data de entrada para processamento: | 170916 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1210/jc.2017-00840 |
|
|