TRβ1 Protein Is Preferentially Expressed in the Pericentral Zone of Rat Liver and Exhibits Marked Diurnal Variation

Doulabi, Behrouz Zandieh; Schiphorst, M. Platvoet-Ter; Beeren, H C van; Labruyère, Wil T.; Lamers, Wouter H.; Fliers, Eric; Bakker, O.; Wiersinga, Wilmar M.

doi:10.1210/endo.143.3.8706

Cited by 43 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the liver, TRs controls physiological functions, such as bile acid homeostasis and ammonia metabolism. TRβ is expressed by perivenous hepatocytes [59], but also by BECs [60]. In rats submitted to BDL, T3 limits the ductular reaction by inhibiting BECs proliferation [60].…”

Section: Nrs In Liver Pathophysiologymentioning

confidence: 99%

Nuclear Receptors in Acute and Chronic Cholestasis

Gonzalez-Sanchez

Firrincieli

Housset

et al. 2015

Dig Dis

View full text Add to dashboard Cite

Background: Nuclear receptors (NRs) form a family of 48 members. NRs control hepatic processes such as bile acid homeostasis, lipid metabolism and mechanisms involved in fibrosis and inflammation. Due to their central role in the regulation of hepatoprotective mechanisms, NRs are promising therapeutic targets in cholestatic disorders. Key Messages: NRs can be classified into five different physiological clusters. NRs from the ‘bile acids and xenobiotic metabolism' and from the ‘lipid metabolism and energy homeostasis' clusters are strongly expressed in the liver. Furthermore, NRs from these clusters, such as farnesoid X receptor α (FXRα), pregnane X receptor (PXR) and peroxisome proliferator-activated receptors (PPARs), have been associated with the pathogenesis and the progression of cholestasis. The latter observation is also true for vitamin D receptor (VDR), which is barely detectable in the whole liver, but has been linked to cholestatic diseases. Involvement of VDR in cholestasis is ascribed to a strong expression in nonparenchymal liver cells, such as biliary epithelial cells, Kupffer cells and hepatic stellate cells. Likewise, NRs from other physiological clusters with low hepatic expression, such as estrogen receptor α (ERα) or reverse-Erb α/β (REV-ERB α/β), may also control pathophysiological processes in cholestasis. Conclusions: In this review, we will describe the impact of individual NRs on cholestasis. We will then discuss the potential role of these transcription factors as therapeutic targets.

show abstract

Section: Nrs In Liver Pathophysiologymentioning

confidence: 99%

Nuclear Receptors in Acute and Chronic Cholestasis

Gonzalez-Sanchez

Firrincieli

Housset

et al. 2015

Dig Dis

View full text Add to dashboard Cite

show abstract

“… 37 An initial study on protein level showed that both receptors are expressed in the liver, with higher levels around the central vein but a broader gradient for TRα. 38 , 39 A more recent study using single-cell RNA sequencing technology supported the presence of both TR isoforms in hepatocytes with only minor differences between perivenous and periportal areas and Thrb expression exceeding Thra . 40 A high-fat diet generally elevated the expression, but primarily increased the levels of Thra in immune cells.…”

Section: Discussionmentioning

confidence: 98%

Lack of thyroid hormone receptor beta is not detrimental for non-alcoholic steatohepatitis progression

Lopez-Alcantara,

Oelkrug,

Sentis

et al. 2023

iScience

View full text Add to dashboard Cite

Hepatic HNF4α deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes

et al. 2007

Self Cite

View full text Add to dashboard Cite

In liver, most genes are expressed with a porto-central gradient. The transcription factor hepatic nuclear-factor4␣ (HNF4␣) is associated with 12% of the genes in adult liver, but its involvement in zonation of gene expression has not been investigated. A putative HNF4␣-response element in the upstream enhancer of glutamine synthetase (GS), an exclusively pericentral enzyme, was protected against DNase-I and interacted with a protein that is recognized by HNF4␣-specific antiserum. Chromatin-immunoprecipitation assays of HNF4␣-deficient (H4LivKO) and control (H4Flox) livers with HNF4␣ antiserum precipitated the GS upstream enhancer DNA only from H4Flox liver. Identical results were obtained with a histone-deacetylase1 (HDAC1) antibody, but antibodies against HDAC3, SMRT and SHP did not precipitate the GS upstream enhancer. In H4Flox liver, GS, ornithine aminotransferase (OAT) and thyroid hormone-receptor ␤1 ( T he development and maintenance of liver architecture and function is regulated by liver-enriched transcription factors. 1 One of these, hepatic nuclear factor 4␣ (HNF4␣; NR2A1) is expressed at high levels in liver, kidney, intestine, and pancreas 2,3 and binds to the promoter of 12% of genes that are expressed in adult liver. 4 HNF4␣ is an orphan member of the nuclear-receptor superfamily. 2 Depending on chain length and degree of saturation, 5 fatty acyl-coenzyme A thioesters may act as agonistic or antagonistic factors, but whether or not these thioesters function as ligands remains unsettled. 2,[6][7][8] Transcriptional regulation by HNF4␣ is accomplished by interactions with coactivator or corepressor mediators (e.g., GRIP1, SRC-1, CBP/p300, SMRT). 6,7,9,10 The resulting coactivator or corepressor complexes have intrinsic histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity, respectively. Histone modifications play an important role in the regulation of the

show abstract

TRβ1 Protein Is Preferentially Expressed in the Pericentral Zone of Rat Liver and Exhibits Marked Diurnal Variation

Cited by 43 publications

References 39 publications

Nuclear Receptors in Acute and Chronic Cholestasis

Nuclear Receptors in Acute and Chronic Cholestasis

Lack of thyroid hormone receptor beta is not detrimental for non-alcoholic steatohepatitis progression

Hepatic HNF4α deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes

Contact Info

Product

Resources

About