Impaired Oxidative Endoplasmic Reticulum Stress Response Caused by Deficiency of Thyroid Hormone Receptor α

Takahashi, Kazuya; Furuya, Fumihiko; Shimura, Hiroki; Kaneshige, Masahiro; Kobayashi, Tetsuro

doi:10.1074/jbc.m113.544122

Cited by 12 publications

(10 citation statements)

References 35 publications

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“…The protocols for Western blot analysis and real-time PCR were previously described 45 . Nuclear or cytoplasmic cell extracts were prepared using the NE-PER kit (PIERCE) according to the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

The ligand-bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor-κB activities

Furuya

Ishii

Tamura

et al. 2017

Sci Rep

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In chronic kidney disease (CKD) patients, inflammation plays a pivotal role in the progression of renal fibrosis. Hypothyroidism is associated with an increased occurrence of atherosclerosis and inflammation, suggesting protective roles of thyroid hormones and their receptors against inflammatory processes. The contribution of thyroid hormone receptors to macrophage differentiation has not been well documented. Here, we focused on the endogenous thyroid hormone receptor α (TRα) in macrophages and examined the role of ligand-bound TRα in macrophage polarization-mediated anti-inflammatory effects. TRα-deficient irradiated chimeric mice showed exacerbated tubulointerstitial injury in a unilateral ureteral obstruction model. Compared with wild-type macrophages, macrophages isolated from the obstructed kidneys of mice lacking TRα displayed increased expression of proinflammatory cytokines that was accompanied by enhanced nuclear translocation of p65. Comparison of TRα-deficient bone marrow-derived macrophages with wild-type macrophages confirmed the propensity of the former cells to produce excessive IL-1β levels. Co-culture of these macrophages with renal epithelial cells induced more severe damage to the epithelial cells via the IL-1 receptor. Our findings indicate that ligand-bound TRα on macrophages plays a protective role in kidney inflammation through the inhibition of NF-κB pathways, possibly by affecting the pro- and anti-inflammatory balance that controls the development of CKD.

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Section: Methodsmentioning

confidence: 99%

The ligand-bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor-κB activities

Furuya

Ishii

Tamura

et al. 2017

Sci Rep

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“…Furthermore, a study showed that TH receptor disorder is closely related to pancreatic β cell survival after endoplasmic reticulum (ER) stress. This study found higher levels of TR α -activated transcription factor 4 (ATF4) and heme oxygenase 1, which facilitates adaptation to oxidative ER stress in the pancreas of HFD-treated mice [ 80 ]. In addition, it is known that glucose sensing is the initial event for glucose-stimulated insulin secretion.…”

Section: Roles Of Thyroid and Thyroid Hormone In Pancreas Pathogenmentioning

confidence: 99%

The Roles of Thyroid and Thyroid Hormone in Pancreas: Physiology and Pathology

Chen

Xie

Shen

et al. 2018

International Journal of Endocrinology

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It is widely accepted that thyroid hormones (THs), secreted from the thyroid, play important roles in energy metabolism. It is also known that THs also alter the functioning of other endocrine glands; however, their effects on pancreatic function have not yet been reviewed. One of the main functions of the pancreas is insulin secretion, which is altered in diabetes. Diabetes, therefore, could be related to thyroid dysfunction. Earlier research on this subject focused on TH regulation of pancreas function (such as insulin secretion) or on insulin function through TH-mediated increase of energy metabolism. Afterwards, epidemiological investigations and animal test research found a link between autoimmune diseases, thyroid dysfunction, and pancreas pathology; however, the underlying mechanisms remain unknown. Furthermore, recent studies have shown that THs also play important roles in pancreas development and on islet pathology, both in diabetes and in pancreatic cancer. Therefore, an overview of the effects of thyroid and THs on pancreas physiology and pathology is presented. The topics contained in this review include a summary of the relationship between autoimmune thyroid dysfunction and autoimmune pancreas lesions and the effects of THs on pancreas development and pancreas pathology (diabetes and pancreatic cancer).

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“…The study was approved by the Animal Research Committee of Kyushu University and carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and experimental procedures were based on the Guidelines of the Committee for Animal Care and Use of Kyushu University. TRa-deficient mice (TRa 0/0), which lack all known products of the TRa gene, were created in the laboratory of Dr. Samarut, as described elsewhere (Macchia et al, 2001;Takahashi et al, 2014). The mice were maintained at the University of Chicago for several generations and back-crossed more than 10 times onto the C57BL/6 background before TRa 0/0 male and female mice were given to Dr. Suzuki's lab (Fukushima Medical University, F, Japan), and were then kindly given to the present authors by Dr. Suzuki with the permission of Dr. Samarut.…”

Section: Animalsmentioning

confidence: 99%

Effects of 3,3',5‐triiodothyronine on microglial functions

Mori

Tomonaga

Калашникова³

et al. 2015

Glia

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L-tri-iodothyronine (3, 3', 5-triiodothyronine; T3) is an active form of the thyroid hormone (TH) essential for the development and function of the CNS. Though nongenomic effect of TH, its plasma membrane-bound receptor, and its signaling has been identified, precise function in each cell type of the CNS remained to be investigated. Clearance of cell debris and apoptotic cells by microglia phagocytosis is a critical step for the restoration of damaged neuron-glia networks. Here we report nongenomic effects of T3 on microglial functions. Exposure to T3 increased migration, membrane ruffling and phagocytosis of primary cultured mouse microglia. Injection of T3 together with stab wound attracted more microglia to the lesion site in vivo. Blocking TH transporters and receptors (TRs) or TRα-knock-out (KO) suppressed T3-induced microglial migration and morphological change. The T3-induced microglial migration or membrane ruffling was attenuated by inhibiting Gi /o -protein as well as NO synthase, and subsequent signaling such as phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). Inhibitors for Na(+) /K(+) -ATPase, reverse mode of Na(+) /Ca(2+) exchanger (NCX), and small-conductance Ca(2+) -dependent K(+) (SK) channel also attenuated microglial migration or phagocytosis. Interestingly, T3-induced microglial migration, but not phagocytosis, was dependent on GABAA and GABAB receptors, though GABA itself did not affect migratory aptitude. Our results demonstrate that T3 modulates multiple functional responses of microglia via multiple complex mechanisms, which may contribute to physiological and/or pathophysiological functions of the CNS.

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Impaired Oxidative Endoplasmic Reticulum Stress Response Caused by Deficiency of Thyroid Hormone Receptor α

Cited by 12 publications

References 35 publications

The ligand-bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor-κB activities

The ligand-bound thyroid hormone receptor in macrophages ameliorates kidney injury via inhibition of nuclear factor-κB activities

The Roles of Thyroid and Thyroid Hormone in Pancreas: Physiology and Pathology

Effects of 3,3',5‐triiodothyronine on microglial functions

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