ArticleJCI insight2023
Perturbation of endoplasmic reticulum proteostasis triggers tissue injury in the thyroid gland.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 8 citations in OpenAlex.
- Substrate for Thyroid Hormone Synthesis: Biochemistry, Evolution, and Physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Article
- Thyroid Hormone Synthesis Without Thyroglobulin.Thyroid : official journal of the American Thyroid Association · 2026Article
- Endoplasmic reticulum stress in Hashimoto's thyroiditis: a candidate amplification node linking thyroid-specific vulnerability and immune dysregulation.Frontiers in immunology · 2026Review
- Thyroidal expression of ER molecular chaperone GRP170 is required for efficient TSH-mediated thyroid hormone synthesis.JCI insight · 2025Article
- VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells.Cell reports · 2025Article
- Coordinated Role of Autophagy and ERAD in Maintaining Neuroendocrine Function by Preventing Prohormone Aggregation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CRABP1 Signalosomes in Non-Canonical Actions of Retinoic Acid-Maintaining Health and Preventing Thyroid Dysfunction in Aging.Endocrines · 2025Article
- Lactoferrin alleviates oxidative stress and endoplasmic reticulum stress induced by autoimmune thyroiditis by modulating the mTOR pathway in the thyroid.Journal of endocrinological investigation · 2025Article
- FVB But Not B6 Mice Carrying the Thr92Ala-Dio2 Polymorphism Have Impaired Thyroid Hormonogenesis and Goiter.Endocrinology · 2025Article
- LINE-1 transposition into murine Thyroglobulin results in congenital thyroid dysplasia.PloS one · 2025Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Defects in endoplasmic reticulum (ER) proteostasis have been linked to diseases in multiple organ systems. Here we examined the impact of perturbation of ER proteostasis in mice bearing thyrocyte-specific knockout of either HRD1 (to disable ER-associated protein degradation [ERAD]) or ATG7 (to disable autophagy) in the absence or presence of heterozygous expression of misfolded mutant thyroglobulin (the most highly expressed thyroid gene product, synthesized in the ER). Misfolding-inducing thyroglobulin mutations are common in humans but are said to yield only autosomal-recessive disease - perhaps because misfolded thyroglobulin protein might undergo disposal by ERAD or ER macroautophagy. We find that as single defects, neither ERAD, nor autophagy, nor heterozygous thyroglobulin misfolding altered circulating thyroxine levels, and neither defective ERAD nor defective autophagy caused any gross morphological change in an otherwise WT thyroid gland. However, heterozygous expression of misfolded thyroglobulin itself triggered significant ER stress and individual thyrocyte death while maintaining integrity of the surrounding thyroid epithelium. In this context, deficiency of ERAD (but not autophagy) resulted in patchy whole-follicle death with follicular collapse and degeneration, accompanied by infiltration of bone marrow-derived macrophages. Perturbation of thyrocyte ER proteostasis is thus a risk factor for both cell death and follicular demise.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.