Thyroid hormone signaling in the intestinal stem cells and their niche

Giolito, Maria Virginia; Plateroti, Michelina

doi:10.1007/s00018-022-04503-y

Cited by 6 publications

(4 citation statements)

References 156 publications

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“…Similar results were obtained in other tissues such as hindlimbs, which appear during metamorphosis ( 19 ), and brain, which is deeply remodeled through neural cell proliferation in ventricular and subventricular zones ( 20 ). THs are also important mediators of cell proliferation in mammals ( 21 ) for cells as diverse as rat pituitary GH-producing cells, which proliferate in response to T 3 by shortening G1 phase ( 22 ), hepatocytes ( 23 ), intestinal epithelial cells ( 24 ), cardiomyocytes ( 25 ), and skin cells ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

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Overlapping action of T3 and T4 during Xenopus laevis development

Tribondeau,

Du Pasquier,

Benchouaia

et al. 2024

Front. Endocrinol.

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Thyroid hormones are involved in many biological processes such as neurogenesis, metabolism, and development. However, compounds called endocrine disruptors can alter thyroid hormone signaling and induce unwanted effects on human and ecosystems health. Regulatory tests have been developed to detect these compounds but need to be significantly improved by proposing novel endpoints and key events. The Xenopus Eleutheroembryonic Thyroid Assay (XETA, OECD test guideline no. 248) is one such test. It is based on Xenopus laevis tadpoles, a particularly sensitive model system for studying the physiology and disruption of thyroid hormone signaling: amphibian metamorphosis is a spectacular (thus easy to monitor) life cycle transition governed by thyroid hormones. With a long-term objective of providing novel molecular markers under XETA settings, we propose first to describe the differential effects of thyroid hormones on gene expression, which, surprisingly, are not known. After thyroid hormones exposure (T3 or T4), whole tadpole RNAs were subjected to transcriptomic analysis. By using standard approaches coupled to system biology, we found similar effects of the two thyroid hormones. They impact the cell cycle and promote the expression of genes involves in cell proliferation. At the level of the whole tadpole, the immune system is also a prime target of thyroid hormone action.

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Section: Discussionmentioning

confidence: 99%

“…(20). THs are also important mediators of cell proliferation in mammals (21) for cells as diverse as rat pituitary GH-producing cells, which proliferate in response to T 3 by shortening G1 phase (22), hepatocytes (23), intestinal epithelial cells (24), cardiomyocytes (25), and skin cells (26).…”

Section: Ths Regulate the Cell Cycle Machinerymentioning

confidence: 99%

Overlapping action of T3 and T4 during Xenopus laevis development

Tribondeau,

Du Pasquier,

Benchouaia

et al. 2024

Front. Endocrinol.

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“…Thyroid hormones not only affect gastrointestinal motor function ( 46 ) but also play a crucial role in maintaining intestinal epithelial homeostasis. Recent studies indicate that thyroid hormones and their receptors perform diverse functions in intestinal stem cells and their niches ( 47 ). Furthermore, the well-documented bidirectional crosstalk between thyroid hormones and the immune response underscores their interplay ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Casual associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines

Wu,

Yi,

2024

Front. Endocrinol.

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BackgroundPrevious observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to investigate the causal association between thyroid function and IBD.MethodsGenome-wide association studies (GWAS) involving seven indicators of thyroid function, IBD, and 41 cytokines were analyzed. Bidirectional two-sample Mendelian randomization (MR) and multivariable MR were conducted to examine the causal relationship between thyroid function and IBD and to explore the potential mechanisms underlying the associations.ResultsGenetically determined hypothyroidism significantly reduced the risk of CD (odds ratio [OR] = 0.761, 95% CI: 0.655–0.882, p < 0.001). Genetically determined reference-range TSH was found to have a suggestive causal effect on IBD (OR = 0.931, 95% CI: 0.888–0.976, p = 0.003), (Crohn disease) CD (OR = 0.915, 95% CI: 0.857–0.977, p = 0.008), and ulcerative colitis (UC) (OR =0.910, 95% CI: 0.830–0.997, p = 0.043). In reverse MR analysis, both IBD and CD appeared to have a suggestive causal effect on the fT3/fT4 ratio (OR = 1.002, p = 0.013 and OR = 1.001, p = 0.015, respectively). Among 41 cytokines, hypothyroidism had a significant impact on interferon-inducible protein-10 (IP-10) (OR = 1.465, 95% CI: 1.094–1.962, p = 0.010). The results of multivariable MR showed that IP-10 may mediate the causal effects of hypothyroidism with CD.ConclusionOur results suggest that an elevated TSH level reduces the risk of CD, with IP-10 potentially mediating this association. This highlights the pituitary-thyroid axis could serve as a potential therapeutic strategy for CD.

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“…Although epidemiologic studies on the involvement of thyroid hormones (TH) in CRC have conflicted, most point towards hyperthyroidism and TH supplementation as predisposing risk factors for CRC (rev. in [ 12 – 16 ]). Our laboratory has contributed to the field by studying the function of the THs and their nuclear hormone receptor TRα1 in intestinal physiology and CRC.…”

Section: Introductionmentioning

confidence: 99%

Impact of the thyroid hormone T3 and its nuclear receptor TRα1 on colon cancer stem cell phenotypes and response to chemotherapies

Giolito,

Bodoirat,

La Rosa

et al. 2024

Cell Death Dis

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Colorectal cancers (CRCs) are highly heterogeneous and show a hierarchical organization, with cancer stem cells (CSCs) responsible for tumor development, maintenance, and drug resistance. Our previous studies showed the importance of thyroid hormone-dependent signaling on intestinal tumor development and progression through action on stem cells. These results have a translational value, given that the thyroid hormone nuclear receptor TRα1 is upregulated in human CRCs, including in the molecular subtypes associated with CSC features. We used an established spheroid model generated from the human colon adenocarcinoma cell line Caco2 to study the effects of T3 and TRα1 on spheroid formation, growth, and response to conventional chemotherapies. Our results show that T3 treatment and/or increased TRα1 expression in spheroids impaired the response to FOLFIRI and conferred a survival advantage. This was achieved by stimulating drug detoxification pathways and increasing ALDH1A1-expressing cells, including CSCs, within spheroids. These results suggest that clinical evaluation of the thyroid axis and assessing TRα1 levels in CRCs could help to select optimal therapeutic regimens for patients with CRC.

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Thyroid hormone signaling in the intestinal stem cells and their niche

Cited by 6 publications

References 156 publications

Overlapping action of T3 and T4 during Xenopus laevis development

Overlapping action of T3 and T4 during Xenopus laevis development

Casual associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines

Impact of the thyroid hormone T3 and its nuclear receptor TRα1 on colon cancer stem cell phenotypes and response to chemotherapies

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