Differentially Expressed Mitochondrial Circulating mRNA in Hypothyroidism Could Be Useful as a Survivor Biomarker in Nonthyroidal Illness Syndrome
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE176153 | GEO | 2021/06/05
REPOSITORIES: GEO
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Project description:Congenital hypothyroidism is a genetic condition in which the thyroid gland fails to produce sufficient thyroid hormone (TH), resulting in metabolic dysfunction and growth retardation. Xb130-/- mice exhibit perturbations of thyrocyte cytoskeleton and polarity, develop postnatal transient growth retardation due to congenital hypothyroidism and leading to multinodular goiter in elderly. To determine the underlying mechanisms, we performed transcriptomic analyses on thyroid glands of mice at three age points – week 2 (W2, before visible growth retardation), W4 (at the nadir of growth), and W12 (immediately before full growth recovery. We compared gene expression between Xb130+/+ and Xb130-/- mice.
2024-10-12 | GSE197052 | GEO
Project description:An imbalance in thyroid hormones (THs) is associated with reversible dementia and Alzheimer’s disease (AD) pathogenesis. Whether hypothyroidism occurs in AD brains and how it affects AD pathology remain largely unknown. Here, we find that reduced conversion of thyroxine (T4) to tri-iodothyronine (T3) in the brain by decreased iodothyronine deiodinase 2 (DIO2) leads to hippocampal hypothyroidism in early AD model mice prior to TH changes in the blood. A TH deficiency causes immune tolerance with decreased phagocytic activity in microglia, thereby aggravating AD pathology. We demonstrate that microglial ecto-5’-nucleotidase (CD73) is reduced in the hypothyroid state and that its inhibition contributes to immune tolerance in microglia. Thus, our data define a molecular mechanism through which decreased conversion of T4 to T3 in the early AD brain, and consequent brain hypothyroidism causes microglial dysfunction and exacerbates AD pathology.
2023-09-01 | GSE219130 | GEO
Project description:An imbalance in thyroid hormones (THs) is associated with reversible dementia and Alzheimer’s disease (AD) pathogenesis. Whether hypothyroidism occurs in AD brains and how it affects AD pathology remain largely unknown. Here, we find that reduced conversion of thyroxine (T4) to tri-iodothyronine (T3) in the brain by decreased iodothyronine deiodinase 2 (DIO2) leads to hippocampal hypothyroidism in early AD model mice prior to TH changes in the blood. A TH deficiency causes immune tolerance with decreased phagocytic activity in microglia, thereby aggravating AD pathology. We demonstrate that microglial ecto-5’-nucleotidase (CD73) is reduced in the hypothyroid state and that its inhibition contributes to immune tolerance in microglia. Thus, our data define a molecular mechanism through which decreased conversion of T4 to T3 in the early AD brain, and consequent brain hypothyroidism causes microglial dysfunction and exacerbates AD pathology.
2023-09-01 | GSE219129 | GEO
Project description:The monocarboxylate transporter 8 (Mct8) protein is a primary T4 and T3 (TH) transporter. Mutations of the MCT8-encoding, SLC16A2 gene alters thyroid function and thyroid hormone metabolism, and severely impairs neurodevelopment (Allan-Herndon-Dudley syndrome, AHDS). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is thought that Mct8 deficiency in mice is compensated by T4 transport through the Slco1c1-encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the Dio2-encoded type 2 deiodinase (D2). The Slc16a2/Slco1c1 (MO) and Slc16a2/Dio2 (MD) double knock out mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, would be more approriate models of AHDS. The goal of this work was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KOs.
2020-12-15 | GSE155185 | GEO
Project description:Differentially Expressed Mitochondrial Circulating mRNA in Hypothyroidism Could Be Useful as a Survivor Biomarker in Nonthyroidal Illness Syndrome
| PRJNA735194 | ENA
Project description:In patients undergoing thyroidectomy one of the goals of post-surgical follow-up is the correct maintenance of thyroid hormone (TH) levels by replacement therapy with levo-thyroxine (LT4). Nevertheless, some patients complain of symptoms of hypothyroidism (memory loss, weight gain, fatigue, depression, and reduced quality of life) despite values of thyroid hormones get the physiological range. Since this recurrent issue, we aim to compare serum proteomic profiles of LT4-euthyroid thyroidectomized patients with stable or reduced post-operative quality of life. Proteomic analysis highlights a different protein profile in serum of patients with reduced quality of life compared to the other although both resulted euthyroid. Differential proteins are involved in coagulation processes, complement system activation and in lipoprotein particles remodeling, that together lead to a pro-inflammatory response. Moreover, a particular protein isoform pattern of apolipoprotein A1 and alpha 1 antitrypsin, was also detected. This study suggests that LT4 replacement therapy might restore euthyroid conditions in thyroidectomized patients but in some cases without re-establish body tissues euthyroidism. This condition is reflected by the serum protein profile that shows a behavior similar to overt hypothyroidism.
2022-04-04 | PXD028378 | Pride
Project description:These libraries reflect a part of a large study. We construct transcriptome libraries, using whole blood circulating RNAs, of four healthy pregnancy (CTL) and preeclamptic women (PEC). In the manuscript, we perform an edgeR three-group analysis comparing the libraries of healthy thyroid pregnancy (HTP), gestational hypothyroidism (GHT) and preeclampsia (PEC). The HTP and GHT libraries are available in GSE147527. As a result, we obtained 1276 DEG in GHT and 1185 DEG in PEC. We also found 195 olfactory receptors common between only in GHT and PEC.
2020-08-31 | GSE157148 | GEO
Project description:Congenital Hypothyroidism occurs in 1:3500 live births and is therefore the most common congenital endocrine disorder. A spectrum of defective thyroid morphology, termed thyroid dysgenesis, represents 80% of permanent CH cases. Although several candidate genes have been implicated in thyroid development, comprehensive screens failed to detect mutation carriers in a significant number of patients with non-syndromic TD. Due to the sporadic occurrence of TD, de novo chromosomal rearrangements are conceivably representing one of the molecular mechanisms participating in its aetiology. Recently, the use of array CGH technique has provided the ability to map these variations genomewide with high resolution. We performed an array CGH screen of 74 TD patients to determine the role of copy number variants (CNV) in the aetiology of the disease. We identified novel CNVs in 8.75% of all patients that have not been described as frequent variations in the healthy population. Affected patients presented with athyreosis or thyroid hypoplasia and in one case with associated heart malformation.
2010-06-01 | GSE18152 | GEO
Project description:We performed a whole-genome DNA methylation analysis (Infinium HumanMethylation450 BeadChip) on peripheral whole blood of 23 twin pairs (10 monozygotic and 13 dizygotic) heterogeneously (4 concordant and 19 discordant) affected by Congenital Hypothyroidism (CH) at birth.
2022-10-03 | GSE161041 | GEO
Project description:Congenital Hypothyroidism occurs in 1:3500 live births and is therefore the most common congenital endocrine disorder. A spectrum of defective thyroid morphology, termed thyroid dysgenesis, represents 80% of permanent CH cases. Although several candidate genes have been implicated in thyroid development, comprehensive screens failed to detect mutation carriers in a significant number of patients with non-syndromic TD. Due to the sporadic occurrence of TD, de novo chromosomal rearrangements are conceivably representing one of the molecular mechanisms participating in its aetiology. Recently, the use of array CGH technique has provided the ability to map these variations genomewide with high resolution. We performed an array CGH screen of 74 TD patients to determine the role of copy number variants (CNV) in the aetiology of the disease. We identified novel CNVs in 8.75% of all patients that have not been described as frequent variations in the healthy population. Affected patients presented with athyreosis or thyroid hypoplasia and in one case with associated heart malformation. We selected 74 patients with thyroid dysgenesis for array CGH analysis. All individuals were detected in neonatal screening programs and abnormal thyroid gland morphology was subsequently confirmed by ultrasound examination. Intragenic mutations in NKX2-1, FOXE1 and NKX2.5 had been previously excluded in phenotype characteristic individuals. PAX8 mutations were excluded in all patients with hypoplastic thyroids by direct sequencing of the coding exons 1-11. The study was approved by the local ethics committee. Genomic DNA of all subjects as well as of healthy controls was isolated from peripheral blood leucocytes using the Qiagen DNA blood mini kit (Qiagen, Hilden, Germany). Array-comparative genomic hybridization was carried as described previously {Erdogan, 2006 #142; Pinkel, 1998 #151}. In brief, sonicated patient- and control DNA was labeled by random priming with Cy3-dUTP and Cy5-dUTP (Bioprime Array CGH, Invitrogen, Carlsbad, CA), respectively, and hybridized onto a submegabase resolution tiling path BAC array, consisting of ~ 36 000 BAC clones obtained from several sources as described elsewhere {Fiegler, 2003 #198; Ishkanian, 2004 #196; Krzywinski, 2004 #197} . Step-by-step protocols are also provided at http://www.molgen.mpg.de/~abt_rop/molecular_cytogenetics/. Arrays were scanned with the G2565BA Agilent Microarray Scanner System (resolution 10 µm; PMT 100 % for Cy3/Cy5, respectively) (Agilent Inc. Santa Clara, CA) and analyzed using GENEPIX Pro 5.0 Software. Analysis and visualization of array CGH data were performed with our software package CGHPRO {Chen, 2005 #143}. For the assessment of copy number gains and losses, we used conservative log2 ratio thresholds of 0.3 and -0.3, respectively. Deviant signal intensity ratios involving three or more consecutive BAC clones were considered to be potentially pathogenic, unless they were covered by more than one known DNA copy number variant, as listed in the Database of Genomic Variants (http://projects.tcag.ca/variation/) or covered by > 50% of their length at least once in our reference set of 600 samples. Potentially pathogenic CNVs were verified by array CGH on a 244k oligonucleotide array from Agilent following the manufacturer’s instructions (Protocol-No. G4410-90010). Confirmed CNVs were tested for inheritance by co-hybridization of parental DNA on BAC arrays as described above. All chromosome coordinates are referring to the UCSC Genome Browser Assembly May 2004 (hg17/ NCBI Build 35; available at: http://genome.ucsc.edu/cgi-bin/hgGateway?hgsid=99195739&clade=vertebrate&org=Human&db=hg17). Cytoscape {Shannon, 2003 #201} was used for the elucidation of potential interactions between genes within the intervals of interest.
2010-05-31 | E-GEOD-18152 | biostudies-arrayexpress