The Expression Profiles of Nuclear Receptors in the Developing and Adult Kidney

Suh, Jae Mi; Yu, Cheng-Tai; Tang, Ke; Tanaka, Toshiya; Kodama, Tatsuhiko; Tsai, Ming‐Jer; Tsai, Sophia Y.

doi:10.1210/me.2006-0312

Cited by 33 publications

(31 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, in HBV transgenic mice, synthesis of the 3.5-kb RNA greatly predominates in hepatocytes and proximal convoluted renal tubules (12). The liver and kidney express not only NR PPAR␣ and HNF4␣ but also FXR␣ (38). Thus, FXR␣ could be another factor implicated in the HBV-restricted tropism at the transcriptional level.…”

Section: Discussionmentioning

confidence: 99%

Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

Ramière

Scholtès

Diaz

et al. 2008

J Virol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) core promoter activity is positively and negatively regulated by nuclear receptors, a superfamily of ligand-activated transcription factors, via cis-acting sequences located in the viral genome. In this study, we investigated the role of farnesoid X receptor alpha (FXR␣) in modulating transcription from the HBV core promoter. FXR␣ is a liver-enriched nuclear receptor activated by bile acids recognizing hormone response elements by forming heterodimers with retinoid X receptor alpha (RXR␣). Electrophoretic mobility shift assays demonstrated that FXR␣-RXR␣ heterodimers can bind two motifs on the HBV enhancer II and core promoter regions, presenting high homology to the consensus (AGGTCA) inverted repeat FXR␣ response elements. In transient transfection of the human hepatoma cell line Huh-7, bile acids enhanced the activity of a luciferase reporter containing the HBV enhancer II and core promoter sequences through FXR␣. Moreover, using a greater-than-genome-length HBV construct, we showed that FXR␣ also increased synthesis of the viral pregenomic RNA and DNA replication intermediates. The data strongly suggest that FXR␣ is another member of the nuclear receptor superfamily implicated in the regulation of HBV core promoter activity and that bile acids could play an important role in the natural history of HBV infection.Hepatitis B virus (HBV) infection is limited to hepatocytes of humans and primates and is associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma (10,19). HBV is an enveloped virus containing a 3.2-kb partially doublestranded DNA genome with four open reading frames. These open reading frames encode the reverse transcriptase, precore, and core proteins; three surface antigen proteins (pre-S1, pre-S2, and S); and the X protein. Regulation of HBV transcription is under the control of four promoters (the core, pre-S1, pre-S2/S, and X promoters) and two enhancer regions (EN1 and EN2). For some authors, the core promoter corresponds to two distinct promoters, namely the precore and pregenomic promoters (44,46). The core promoter activity, modulated by the EN2 region, plays a critical role in the virus life cycle. It initiates the synthesis of the precore and pregenomic 3.5-kb RNAs. The precore RNA encodes the precore protein, also called HBe antigen. The pregenomic RNA encodes both the polymerase and the core protein and serves as the template for viral DNA synthesis (24, 34).Multiple cellular transcription factor binding sites have been identified on these regulatory sequences (26,29,31,40,48,51), in particular for several nuclear receptors (NR) belonging to the superfamily of ligand-activated transcription factors (1,11,13,14,22,23). Two important NR response elements (NRRE), situated in the EN2 (NRRE enhII ) and the core promoter (NRRE pre-C ) regions, are recognized by hepatocyte nuclear factor 4 alpha (HNF4␣) and RXR␣-peroxisome proliferatoractivated receptor alpha (PPAR␣) heterodimers (13,30,44).In hepatoma cell lines, HNF4␣ and PPAR␣-RXR␣ upregulate synthes...

show abstract

Section: Discussionmentioning

confidence: 99%

Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

Ramière

Scholtès

Diaz

et al. 2008

J Virol

View full text Add to dashboard Cite

show abstract

“…Therefore, it seems likely that locally produced aldosterone stimulates the transcription rates of mineralocorticoid-responsive genes by activating MR in mesangial cells (28). MR expression was also detected in podocytes (24,29) and renal tubular cells (20,30,31). Taken together, MR is localized not only in distal tubular cells but also in other renal cells, which mediate aldosterone-induced renal tissue injury.…”

Section: Localization Of Mr In the Kidneymentioning

confidence: 91%

Possible Underlying Mechanisms Responsible for Aldosterone and Mineralocorticoid Receptor–Dependent Renal Injury

et al. 2008

View full text Add to dashboard Cite

Abstract. There is increasing evidence indicating the roles of aldosterone and mineralocorticoid receptor (MR) in the pathogenesis of renal injury. In rats, chronic treatment with aldosterone and salt results in severe proteinuria and renal tissue injury, characterized by glomerulosclerosis and tubulointerstitial fibrosis. Aldosterone-induced renal tissue injury is associated with increases in reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs) or Rho-kinase. Treatment with a selective MR antagonist, eplerenone, prevents aldosterone-induced increases in ROS levels and MAPK activity and ameliorates renal injury. In vitro studies have revealed that MR is highly expressed in glomerular mesangial cells (RMCs), podocytes, and renal interstitial fibroblasts. In these renal cells, aldosterone induces cellular injury through NADPH oxidase-dependent ROS production and activation of MAPKs or Rhokinase. Such aldosterone-induced renal cellular injury is markedly attenuated by treatment with eplerenone. These data suggest that aldosterone induces renal injury via activation of MR through mechanisms that cannot be simply explained by changes in blood pressure. In this review, we summarized recent findings on the roles of aldosterone and MR in the pathogenesis of renal injury with particular emphasis on potential underlying mechanisms.

show abstract

“…2 A). To clarify the distribution of COUP-TFII protein, we performed immunohistochemistry on E13.5 horizontal sections with an antibody that had been shown to be specific for COUP-TFII in the previous study (Suh et al, 2006). A strong COUP-TFII signal was detected in the CGE, and a moderate signal was observed in the caudal cortex (Fig.…”

Section: Coup-tfii Is Highly Enriched In the Cgementioning

confidence: 94%

COUP-TFII Is Preferentially Expressed in the Caudal Ganglionic Eminence and Is Involved in the Caudal Migratory Stream

Kanatani¹,

Yozu²,

Tabata³

et al. 2008

J. Neurosci.

150

184

View full text Add to dashboard Cite

While the cortical interneurons derived from the medial ganglionic eminence (MGE) migrate rather diffusely into the cortex, interneurons that migrate out from the caudal ganglionic eminence (CGE) mainly move caudally into the caudal cerebral cortex and the hippocampus in the form of the caudal migratory stream (CMS) (Yozu et al., 2005). Although transplantation experiments at embryonic day 13.5 had revealed that the migrating cells in these two populations are already intrinsically different in regard to their ability to respond to the CGE environment (Yozu et al., 2005), it is not known how the CGE cells are specified and how their migratory behavior is determined.In this study we showed that, although CGE and lateral ganglionic eminence (LGE) express almost the same marker molecules, LGE cells do not migrate caudally when transplanted into the CGE, suggesting that LGE cells are intrinsically different from CGE cells. We therefore compared the transcriptomes of the CGE, MGE, and LGE, and the results showed that COUP-TFII was expressed preferentially in the CGE as well as in the migrating interneurons in the CMS. Transplantation experiments revealed that COUP-TFII is sufficient to change the direction of MGE cell migration to caudal when transplanted into the CGE environment, and knockdown of COUP-TFII inhibited the caudal migration of the CGE cells. These results suggest that COUP-TFII is both required and sufficient for the CGE-cellspecific migratory behavior in the caudal direction. Thus, a locally expressed transcription factor determines the migratory direction of the cortical interneurons in a region-specific manner.

show abstract

The Expression Profiles of Nuclear Receptors in the Developing and Adult Kidney

Cited by 33 publications

References 22 publications

Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

Possible Underlying Mechanisms Responsible for Aldosterone and Mineralocorticoid Receptor–Dependent Renal Injury

COUP-TFII Is Preferentially Expressed in the Caudal Ganglionic Eminence and Is Involved in the Caudal Migratory Stream

Contact Info

Product

Resources

About