Thyroid Hormone receptor regulates hepatic stellate cell activation

Manka, PP; Coombes, Jason D.; Bechmann, Lars P.; Dollé, Laurent; Swiderska‐Syn, Marzena; Briones-Orta, Marco A.; Rb, Williams; Grunsven, Leo van; Canbay, A; Flamant, Frédéric; Gauthier, Karine; Syn, WK

doi:10.1016/s0168-8278(17)31587-8

Cited by 15 publications

(26 citation statements)

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“…3,4,7 In addition, some investigators have hypothesized that the thyroid hormone receptor may activate hepatic stellate cells and hepatic fibrogenesis. 8 The causal relationship could not be determined owing to study design. Although noninvasive fibrosis markers were broadly validated, advanced fibrosis may be underestimated.…”

Section: Discussionmentioning

confidence: 99%

Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States

Kim

Yoo

et al. 2019

Clinical Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 99%

Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States

Kim

Yoo

et al. 2019

Clinical Gastroenterology and Hepatology

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“…This gives rise to mitochondrial dysfunction and an increase in free fatty acids and ROS, leading to lipid peroxidation, activation of Kupffer cells and Hepatic Stellate Cells. In the case of hepatic injury, expression of the nuclear thyroid hormone receptor in Hepatic Stellate Cells is inhibited, and the dominant hormone receptor becomes TRα, which participates in the fibrogenic response, producing a stronger wound-healing response and higher contractility (34). The levels of inflammatory cytokines increase, causing a further increase in ROS formation, impairment of deiodinase activity, an increase in cell proliferation, and ultimately fibrosis leading to cancer, as will be described in the following sections [(20, 35); Figure 2].…”

Section: Thyroid Hormones and Liver Diseasementioning

confidence: 99%

The Role of Thyroid Hormones in Hepatocyte Proliferation and Liver Cancer

et al. 2019

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Thyroid hormones T3 and T4 (thyroxine) control a wide variety of effects related to development, differentiation, growth and metabolism, through their interaction with nuclear receptors. But thyroid hormones also produce non-genomic effects that typically start at the plasma membrane and are mediated mainly by integrin αvβ3, although other receptors such as TRα and TRβ are also able to elicit non-genomic responses. In the liver, the effects of thyroid hormones appear to be particularly important. The liver is able to regenerate, but it is subject to pathologies that may lead to cancer, such as fibrosis, cirrhosis, and non-alcoholic fatty liver disease. In addition, cancer cells undergo a reprogramming of their metabolism, resulting in drastic changes such as aerobic glycolysis instead of oxidative phosphorylation. As a consequence, the pyruvate kinase isoform M2, the rate-limiting enzyme of glycolysis, is dysregulated, and this is considered an important factor in tumorigenesis. Redox equilibrium is also important, in fact cancer cells give rise to the production of more reactive oxygen species (ROS) than normal cells. This increase may favor the survival and propagation of cancer cells. We evaluate the possible mechanisms involving the plasma membrane receptor integrin αvβ3 that may lead to cancer progression. Studying diseases that affect the liver and their experimental models may help to unravel the cellular pathways mediated by integrin αvβ3 that can lead to liver cancer. Inhibitors of integrin αvβ3 might represent a future therapeutic tool against liver cancer. We also include information on the possible role of exosomes in liver cancer, as well as on recent strategies such as organoids and spheroids, which may provide a new tool for research, drug discovery, and personalized medicine.

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“…Increased serum TSH levels induce liver triglyceride accumulation, mainly via up-regulation of SREBP-1 stimulated by TSH receptors, resulting in induction of NAFLD [188]. In a recent study of a methionine–choline-deficient murine model, thyroid hormone receptor knock-out mice showed an enhanced response to TGF-ß in hepatic stellate cells, suggesting a potential role of thyroid hormone signaling in hepatic fibrogenesis [189]. Other studies also demonstrated that low thyroid hormones levels may alter hepatic fatty acid composition and glycogen accumulation, decreasing the activity of acetyl-CoA carboxylase 1 and fatty acid synthase [190,191].…”

Section: Resultsmentioning

confidence: 99%

“…EndocrinopathiesPolycystic ovarian syndromeHypothyroidismObesity and IR are common risk factors for both PCOS and NAFLD [207,208,209,210]. The prevalence of NAFLD is higher in patients with hypothyroidism; furthermore, low thyroid function seems to worsen the progression of liver damage, while replacement therapy may improve liver function [187,188,189,194,195,196,197]. Emerging LinkagesOsteoporosisNAFLD is associated with a 2.5-fold risk of osteoporotic fractures [122,124,125].…”

Section: Table A1mentioning

confidence: 99%

NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome

Rosato

Masarone

Dallio

et al. 2019

IJERPH

104

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.

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Thyroid Hormone receptor regulates hepatic stellate cell activation

Cited by 15 publications

References 0 publications

Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States

Low-Normal Thyroid Function Is Associated With Advanced Fibrosis Among Adults in the United States

The Role of Thyroid Hormones in Hepatocyte Proliferation and Liver Cancer

NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome

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