Insight Into Mouse Models of Hyperthyroidism

Zhang, Mengyu; Jiang, Wen; Gui, Lu; Wang, Ru; Lv, Zhongwei; Li, Dan

doi:10.3389/fendo.2022.929750

Cited by 11 publications

(7 citation statements)

References 47 publications

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“…Indeed, in our plasmid-immunized mice model, the orbital tissue and thyroid gland showed different degrees of T lymphocyte and macrophage infiltration, although only 4/6 mice developed ocular symptoms, all of them had varying degrees of elevated thyroid hormone and antibody levels. In addition, a representative TAO mice would show weight loss, 29 which is also present in our model. Of note, the mice treated by dexamethasone had abnormal weight gain, which may be associated with the side effect of glucocorticoid.…”

Section: Discussionmentioning

confidence: 89%

TSG6 Plays a Role in Improving Orbital Inflammatory Infiltration and Extracellular Matrix Accumulation in TAO Model Mice

He¹,

Chen²,

Wang³

et al. 2023

JIR

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Introduction TSG-6 plays a wide anti-inflammatory and therapeutic role in a variety of autoimmune diseases as the key mediator of mesenchymal stem cells (MSCs). Purpose We aimed to test whether TSG-6 could exert similar effects as MSCS in TAO via establishing TAO animal model immunized by hTSHR-A subunit plasmid. Material and Methods We tested the expression level of TSG-6 on intraconal orbital fat from controls and patients with TAO. We established a stable thyroid-associated ophthalmopathy animal model by immunizing 6-week-old female Balb/c mice with recombination hTSHR-A subunit plasmid. After four immunizations, TSG-6 or dexamethasone was injected through the tail vein. The effects of the drugs on body weight, thyroid function, orbital inflammation, fibrosis and lipogenesis were observed. Results The expression of TSG-6 in the orbital tissues of TAO patient is lower than that of normal people. In our animal model, mice showed weight loss, higher TT4 and TSHR antibody levels, and ocular symptoms such as inflammation and proptosis. TSG-6 can reduce ocular fibrosis and lipogenesis by inhibiting the infiltration of CD3+ T lymphocytes and macrophages in the mouse model of thyroid associated ophthalmopathy. Compared with dexamethasone, TSG-6 showed comparable anti-inflammatory effect, moreover, it has given a better performance in inhibiting adipogenesis. Conclusion It was demonstrated that TSG-6 has a considerable positive impact on improving eye symptoms of TAO mice, which could be a novel candidate for the early treatment of TAO.

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Section: Discussionmentioning

confidence: 89%

TSG6 Plays a Role in Improving Orbital Inflammatory Infiltration and Extracellular Matrix Accumulation in TAO Model Mice

He¹,

Chen²,

Wang³

et al. 2023

JIR

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“…Several murine models of hyperthyroidism have been generated through immunization with TSHR protein (20, 21). Interestingly, Jaeschke et al generated mice with a knocked-in human TSHR sequence that had a constitutively active mutation (29).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Landscape of Hyperthyroidism in Mice Overexpressing Thyroid Stimulating Hormone

Yamauchi,

Sugawa,

Hakata

et al. 2023

Preprint

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Hyperthyroidism is a condition with excessive thyroid hormone secretion. Activation of thyroid stimulating hormone receptor (TSHR) fundamentally leads to hyperthyroidism. The details of TSHR signaling remain to be elucidated. We conducted transcriptome analyses for hyperthyroid mice that we generated by overexpressing TSH. TSH overexpression via hydrodynamic gene delivery with pLIVE-TSHBand pLIVE-CGAvectors consistently caused hyperthyroidism and goiters for at least 4 weeks in C57BL/6J mice. RNA sequencing analysis of their thyroid glands revealed that thiamazole slightly changed the thyroid transcriptome, which reinforces a conventional theory that thiamazole decreases thyroid hormone secretion via inhibition of thyroid peroxidase activity. Meanwhile, TSH overexpression drastically changed the thyroid transcriptome. In particular, enrichment analyses identified the cell cycle, phosphatidylinositol-3 kinase/Akt pathway, and Ras-related protein 1 pathway as possibly associated with goiter development. Regarding the role of TSHR signaling in hyperthyroidism, it is noteworthy thatSlc26a4was exclusively upregulated among genes crucial to thyroid hormone secretion at both 1 and 4 weeks after hydrodynamic gene delivery. To verify the relationship between this upregulation and hyperthyroidism, we overexpressed TSH inSlc26a4knockout mice. TSH overexpression caused hyperthyroidism inSlc26a4knockout mice, equivalent to that in control mice. To summarize, we analyzed hyperthyroid mice generated by TSH overexpression. We did not observe significant changes in known genes and pathways involved in thyroid hormone secretion. Thus, our datasets might include candidate genes that have not yet been identified as regulators of thyroid function. Our transcriptome datasets regarding hyperthyroidism can contribute to future research on TSHR signaling.

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“…Xenograft mouse model is extensively used in antitumor drug screening and evaluation (Jin et al, 2023;Wang et al, 2023;Zhang et al, 2023). A schematic diagram was used to show the experimental protocol.…”

Section: Fndc5 Inhibits Tumor Growth Of Xenograft Mouse Modelmentioning

confidence: 99%

FNDC5 inhibits malignant growth of human cervical cancer cells via restraining PI3K/AKT pathway

Li,

Wang,

et al. 2024

Journal Cellular Physiology

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Cervical cancer (CxCa) is the fourth most frequent cancer in women. This study aimed to determine the role and underlying mechanism of fibronectin type III domain‐containing protein 5 (FNDC5) in inhibiting CxCa growth. Experiments were performed in human CxCa tissues, human CxCa cell lines (HeLa and SiHa), and xenograft mouse model established by subcutaneous injection of SiHa cells in nude mice. Bioinformatics analysis showed that CxCa patients with high FNDC5 levels have a longer overall survival period. FNDC5 expression was increased in human CxCa tissues, HeLa and SiHa cells. FNDC5 overexpression or FNDC5 protein not only inhibited proliferation, but also restrained invasion and migration of HeLa and SiHa cells. The effects of FNDC5 were prevented by inhibiting integrin with cilengitide, activating PI3K with recilisib or activating Akt with SC79. FNDC5 inhibited the phosphorylation of PI3K and Akt, which was attenuated by recilisib. PI3K inhibitor LY294002 showed similar effects to FNDC5 in HeLa and SiHa cells. Intravenous injection of FNDC5 (20 μg/day) for 14 days inhibited the tumor growth, and reduced the proliferation marker Ki67 expression and the Akt phosphorylation in the CxCa xenograft mouse model. These results indicate that FNDC5 inhibits the malignant phenotype of CxCa cells through restraining PI3K/Akt signaling. Upregulation of FNDC5 may play a beneficial role in retarding the tumor growth of CxCa.

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Insight Into Mouse Models of Hyperthyroidism

Cited by 11 publications

References 47 publications

TSG6 Plays a Role in Improving Orbital Inflammatory Infiltration and Extracellular Matrix Accumulation in TAO Model Mice

TSG6 Plays a Role in Improving Orbital Inflammatory Infiltration and Extracellular Matrix Accumulation in TAO Model Mice

Transcriptomic Landscape of Hyperthyroidism in Mice Overexpressing Thyroid Stimulating Hormone

FNDC5 inhibits malignant growth of human cervical cancer cells via restraining PI3K/AKT pathway

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