Iodotyrosines Are Biomarkers for Preclinical Stages of Iodine-Deficient Hypothyroidism in <i>Dehal1</i>-Knockout Mice

González‐Guerrero, Cristian; Borsò, Marco; Alikhani, Pouya; Alcaina, Yago; Lucia, Federico Salas; Liao, Xiao-Hui; García-Giménez, Jorge; Bertolini, Andrea; Martín, Diana; Moratilla, Adrian; Mora, Roberto; Buño‐Soto, Antonio; Mani, AR; Bernal, Juan; Miguel, María P. De; Refetoff, Samuel; Zucchi, Riccardo; Moreno, J.C.

doi:10.1089/thy.2022.0537

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…Total RNA was extracted from 4 COs per group and treatment. mRNAs were treated with DNase (QIAGEN) and measured by quantitative real-time PCR as previously described ( 95 ). Briefly, total RNA was isolated using a QIAGEN RNeasy Mini Kit, according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Salas-Lucia,

Escamilla,

Bianco

et al. 2024

JCI Insight

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Patients with mutations in the thyroid hormone (TH) cell transporter monocarboxylate transporter 8 ( MCT8 ) gene develop severe neuropsychomotor retardation known as Allan-Herndon-Dudley syndrome (AHDS). It is assumed that this is caused by a reduction in TH signaling in the developing brain during both intrauterine and postnatal developmental stages, and treatment remains understandably challenging. Given species differences in brain TH transporters and the limitations of studies in mice, we generated cerebral organoids (COs) using human induced pluripotent stem cells (iPSCs) from MCT8-deficient patients. MCT8-deficient COs exhibited (i) altered early neurodevelopment, resulting in smaller neural rosettes with thinner cortical units, (ii) impaired triiodothyronine (T3) transport in developing neural cells, as assessed through deiodinase-3–mediated T3 catabolism, (iii) reduced expression of genes involved in cerebral cortex development, and (iv) reduced T3 inducibility of TH-regulated genes. In contrast, the TH analogs 3,5-diiodothyropropionic acid and 3,3′,5-triiodothyroacetic acid triggered normal responses (induction/repression of T3-responsive genes) in MCT8-deficient COs, constituting proof of concept that lack of T3 transport underlies the pathophysiology of AHDS and demonstrating the clinical potential for TH analogs to be used in treating patients with AHDS. MCT8-deficient COs represent a species-specific relevant preclinical model that can be utilized to screen drugs with potential benefits as personalized therapeutics for patients with AHDS.

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Section: Methodsmentioning

confidence: 99%

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Salas-Lucia,

Escamilla,

Bianco

et al. 2024

JCI Insight

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“…Immunofluorescence analysis for STAT-3 was performed as previously described [ 32 ]. The primary antibodies were monoclonal anti-STAT-3 (Stat3 (F-2): sc-8019) (diluted 1:100 in PBS, Santa Cruz Biotechnology, Santa Cruz, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Effects of nicotine on microRNA-124 expression in bile duct ligation-induced liver fibrosis in rats

Hajiasgharzadeh,

Shahabi,

Karimi-Sales

et al. 2024

BMC Pharmacol Toxicol

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Background Nicotine, the main compound of smoking may exert its effects by changing the expression of microRNAs (miRNAs). This study was conducted to further investigate the molecular mechanisms of miRNA-dependent effects of nicotine in an animal model of liver fibrosis. Methods The bile duct ligation (BDL) approach was used to create a model of liver fibrosis. Twenty-four male Wistar rats were used in the study. The effects of nicotine administration on miRNA-124 expression, as well as alpha-smooth muscle actin (liver fibrosis marker) and chemokine ligand 2 (an inflammatory chemokine), were investigated using RT-qPCR. In addition, the mRNA and protein expression of signal transducer and activator of transcription 3 (STAT-3; as a potential target for miRNA-124) were investigated by RT-qPCR and immunofluorescence, respectively. Liver enzyme activity levels were measured using a colorimetric assay. In addition, the effects of nicotine on the process of liver fibrosis were investigated with histological studies. Results The development of liver fibrosis in BDL rats and nicotine administration led to a decrease in miRNA-124 expression. The decrease in the expression is accompanied by the increase in the expression of fibrotic and proinflammatory genes. Also, an increase in STAT-3 mRNA and protein expression was observed in the fibrotic rats that received nicotine. In addition, the significant increase in bilirubin and liver enzymes in fibrotic rats worsens with nicotine administration. The results of histological studies also confirm these results. Conclusion Considering that miRNA-124 is an anti-inflammatory miRNA, it can be concluded that the decrease in its expression due to nicotine exposure leads to an increase in inflammatory processes and subsequently to an increase in liver fibrosis.

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The growing complexity of the control of the hypothalamic pituitary thyroid axis and brown adipose tissue by leptin

Costa-e-Sousa,

Brooks

2024

Vitamins and Hormones

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Iodotyrosines Are Biomarkers for Preclinical Stages of Iodine-Deficient Hypothyroidism in Dehal1-Knockout Mice

Cited by 7 publications

References 28 publications

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome

Effects of nicotine on microRNA-124 expression in bile duct ligation-induced liver fibrosis in rats

The growing complexity of the control of the hypothalamic pituitary thyroid axis and brown adipose tissue by leptin

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