Thyroid hormone's action on progenitor/stem cell biology: New challenge for a classic hormone?

Sirakov, M; Skah, Seham; Nadjar, Julien; Plateroti, Michelina

doi:10.1016/j.bbagen.2012.07.014

Cited by 38 publications

(26 citation statements)

References 144 publications

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“…THs are well-known stimulators of cell proliferation (Sirakov et al, 2012), including neural progenitors (Mohan et al, 2012). The present study contributes the key finding that the stimulation of neural progenitor proliferation by THs is mediated by the TH cell surface receptor itgαvβ3.…”

Section: Discussionmentioning

confidence: 56%

Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex

et al. 2014

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Neocortex expansion during evolution is associated with the enlargement of the embryonic subventricular zone, which reflects an increased self-renewal and proliferation of basal progenitors. In contrast to human, the vast majority of mouse basal progenitors lack self-renewal capacity, possibly due to lack of a basal process contacting the basal lamina and downregulation of cell-autonomous production of extracellular matrix (ECM) constituents. Here we show that targeted activation of the ECM receptor integrin α v β 3 on basal progenitors in embryonic mouse neocortex promotes their expansion. Specifically, integrin α v β 3 activation causes an increased cell cycle reentry of Pax6-negative, Tbr2-positive intermediate progenitors, rather than basal radial glia, and a decrease in the proportion of intermediate progenitors committed to neurogenic division. Interestingly, integrin α v β 3 is the only known cell surface receptor for thyroid hormones. Remarkably, tetrac, a thyroid hormone analog that inhibits the binding of thyroid hormones to integrin α v β 3 , completely abolishes the intermediate progenitor expansion observed upon targeted integrin α v β 3 activation, indicating that this expansion requires the binding of thyroid hormones to integrin α v β 3 . Convergence of ECM and thyroid hormones on integrin α v β 3 thus appears to be crucial for cortical progenitor proliferation and self-renewal, and hence for normal brain development and the evolutionary expansion of the neocortex.

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Section: Discussionmentioning

confidence: 56%

Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex

et al. 2014

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“…Moreover, THs play a significant role in the differentiation of the vast majority of somatic cells (Obregon, 2008;Sirakov et al, 2013). Interestingly, during the last years, extensive research has focused on the role of TH in the differentiation, maturation and functionality of metabolic tissues (Mastracci and Evans-Molina, 2014).…”

Section: Introductionmentioning

confidence: 99%

Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice

López-Noriega

Cobo-Vuilleumier

Narbona-Pérez

et al. 2017

British J Pharmacology

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Thyroid hormones induce several changes in whole body metabolism that are known to improve metabolic homeostasis. However, adverse side effects have prevented its use in the clinic. In view of the promising effects of thyroid hormones, we investigated the effects of levothyroxine supplementation on glucose homeostasis. EXPERIMENTAL APPROACHC57BL/6 mice were treated with levothyroxine from birth to 24 weeks of age, when mice were killed. The effects of levothyroxine supplementation on metabolic health were determined. C57BL/6 mice treated with levothyroxine for 2 weeks and then challenged with streptozotocin to monitor survival. Mechanistic experiments were conducted in the pancreas, liver and skeletal muscle. RIP-B7.1 mice were treated with levothyroxine for 2 weeks and were subsequently immunized to trigger experimental autoimmune diabetes (EAD). Metabolic tests were performed. Mice were killed and metabolic tissues were extracted for immunohistological analyses. KEY RESULTSLong-term levothyroxine supplementation enhanced glucose clearance and reduced circulating glucose in C57BL/6 mice. Levothyroxine increased simultaneously the proliferation and apoptosis of pancreatic beta cells, promoting the maintenance of a highly insulin-expressing beta cell population. Levothyroxine increased circulating insulin levels, inducing sustained activation of IRS1-AKT signalling in insulin-target tissues. Levothyroxine-treated C57BL/6 mice challenged with streptozotocin exhibited extended survival. Levothyroxine blunted the onset of EAD in RIP-B7.1 mice by inducing beta cell proliferation and preservation of insulin-expressing cells. CONCLUSIONS AND IMPLICATIONSInterventions based on the use of thyroid hormones or thyromimetics could be explored to provide therapeutic benefit in patients with type 1 diabetes mellitus.

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“…T3 is a pleiotropic hormone, which controls several cellular processes, including growth, development, and homeostasis (1). The main thyroid product thyroxine (T4) is inactive until converted into the active hormone T3 via type 1 or type 2 deiodinase (D1 and D2), while type 3 deiodinase (D3) converts T4 and T3 into inactive metabolites (2,3).…”

Section: Introductionmentioning

confidence: 99%

Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling

et al. 2016

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Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). Thyroid hormone concentrations in the blood are stable, but the action of the deiodinases (D2-D3) provides cell-specific regulation of thyroid hormone activity. Deregulation of deiodinase function and thyroid hormone status has been implicated in tumorigenesis. Therefore, we investigated the role of thyroid hormone metabolism and signaling in colorectal CSCs (CR-CSC), where deiodinases control cell division and chemosensitivity. We found that increased intracellular thyroid hormone concentration through D3 depletion induced cell differentiation and sharply mitigated tumor formation. Upregulated BMP4 expression and concomitantly attenuated Wnt signaling accompanied these effects. Furthermore, we demonstrate that BMP4 is a direct thyroid hormone target and is involved in a positive autoregulatory feedback loop that modulates thyroid hormone signaling. Collectively, our findings highlight a cell-autonomous metabolic mechanism by which CR-CSCs exploit thyroid hormone signaling to facilitate their self-renewal potential and suggest that druginduced cell differentiation may represent a promising therapy for preventing CSC expansion and tumor progression. Cancer Res; 76(5); 1237-44. Ó2015 AACR.

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Thyroid hormone's action on progenitor/stem cell biology: New challenge for a classic hormone?

Cited by 38 publications

References 144 publications

Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex

Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex

Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice

Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling

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