Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by sphingosine 1-phosphate in HepG2 liver cells

Iwaki, Soichiro; Yamamura, Shuhei; Asai, Moyoko; Sobel, Burton E.; Fujii, Satoshi

doi:10.1016/j.bbagrm.2012.07.001

Cited by 13 publications

(15 citation statements)

References 39 publications

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“…PAI-1 is a major physiological inhibitor of fibrinolysis in the blood and its increased expression has been implicated as a risk factor for myocardial infarction (32, 33). In HepG2 cells, a hepatocarcinoma cell line similar to Huh7 cells used in this study, it was shown that SERBP1 upregulation lead to decreased expression of PAI-1 (34). Although PAI-1 levels were not measured in this study, our LRH1 siRNA experiment suggests that a similar effect on PAI-1 would have been seen since SERBP1 expression was significantly increased.…”

Section: Discussionmentioning

confidence: 84%

SERBP1 Is a Component of the Liver Receptor Homologue-1 Transcriptional Complex

et al. 2015

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Liver receptor homolog-1 (LRH1) is an orphan nuclear receptor that has been shown to play a role in the transcriptional regulation of pathways involved in cancer. Elucidating the components of the LRH1 transcriptional complex to better understand endogenous regulation of the receptor as well as its role in cancer remains a high priority. A sub-cellular enrichment strategy coupled with proteomic approaches was employed to identify putative LRH1 coregulators. Nuclear fractionation protocol was essential for detection of LRH1 peptides by mass spectrometry (MS), with most peptides being observed in the insoluble fraction (receptor bound to DNA). SERBP1 and ILF3 were identified as LRH1 interacting partners by both western blot and MS/MS analysis. Receptor knockdown by siRNA showed an increased in SERBP1 expression while ILF3 expression was unchanged. In contrast, receptor overexpression decreased only SERBP1 mRNA levels. Consistent with these data, in a promoter:reporter assay, binding of LRH1 to the promoter region of SERBP1 resulted in a decrease in the expression level of the reporter gene, and subsequently, inhibiting transcription. Given the receptor’s role in cancer progression, the study here elucidates additional transcriptional machinery involved in LRH1 signaling and potentially provides new targets for therapeutics development.

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Section: Discussionmentioning

confidence: 84%

SERBP1 Is a Component of the Liver Receptor Homologue-1 Transcriptional Complex

et al. 2015

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“…The plasmids used were gifts from Dr Imagawa (Department of Cardiovascular Medicine, Hokkaido University, Sapporo, Japan). pGL3-basic vector (Promega Corporation, Madison, WI, USA) containing the PAI-1 gene promoter region (-825 to +42) (designated as P-1) was used as previously described (5). PAI-1 gene promoter area fragments (P-2, -659 to +42; P-3, -536 to +42; P-4, -360 to +42; P-5, -302 to +42; P-6, -205 to +42; P-7, -165 to +42; P-8, -115 to +42 and P-9, -60 to +42) were constructed in pGL3-control vectors (Promega Corporation) (17,18).…”

Section: Methodsmentioning

confidence: 99%

“…Our previous study demonstrated that in the human HepG2 liver cell line, sphingosine 1-phosphate (S1P) can promptly increase the transcription of PAI-1 (5). S1P, synthesized by sphingosine kinase (SPHK) acting on sphingosine, is a bioactive signaling molecule that regulates cell movement, differentiation, inflammation, angiogenesis and immunity through S1P receptors (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Sphingosine 1-phosphate induced by hypoxia increases the expression of PAI-1 in HepG2 cells via HIF-1α

Sanagawa

Iwaki

Asai

et al. 2016

Molecular Medicine Reports

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Our group has recently reported that in the immortal human HepG2 liver cell line, sphingosine 1‑phosphate (S1P) increases transcription of plasminogen activator inhibitor type‑1 (PAI‑1), the major physiological inhibitor of fibrinolysis, within 4 h. The present study aimed to elucidate the molecular mechanisms underlying this effect. PAI‑1 expression was measured by reverse transcription‑quantitative polymerase chain reaction and immunoblotting. It was demonstrated that S1P increased PAI‑1 promoter activity but did not increase the activity of promoters lacking the hypoxia responsive element (HRE) 2. In addition, S1P transiently increased the concentration of hypoxia inducible factor (HIF)‑1α, a transcription factor capable of binding to HRE. When HIF‑1α was knocked down, the induction of transcription of PAI‑1 by S1P was no longer observed. Sphingosine kinase (SPHK) activity is increased by hypoxia. It was demonstrated that increases in the concentration of the HIF‑1α protein induced by hypoxia were prevented by treatment with SPHK inhibitor or S1P receptor antagonists. Thus, modification of the induction of HIF‑1α by S1P, leading to increased transcription of PAI‑1, may be an attractive therapeutic target for thrombosis and consequent inhibition of fibrinolysis associated with hypoxia.

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“…(72–74)). Studies in a number of cell lines that shown that elevation of intracellular cAMP levels markedly increases the rate of degradation of PAI-1 mRNA, which has been shown to be mediated by SERBP1 (73;75). Like HABP4, SERBP1 binds to CHD-3, which for SERBP1 involves two separate regions, located in its N- and C-termini (76;77).…”

Section: Introductionmentioning

confidence: 99%

The RNA-binding protein SERBP1 interacts selectively with the signaling protein RACK1

Bolger

2017

Cellular Signalling

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The RACK1 protein interacts with numerous proteins involved in signal transduction, the cytoskeleton, and mRNA splicing and translation. We used the 2-hybrid system to identify additional proteins interacting with RACK1 and isolated the RNA-binding protein SERBP1. SERPB1 shares amino acid sequence homology with HABP4 (also known as Ki-1/57), a component of the RNA spicing machinery that has been shown previously to interact with RACK1. Several different isoforms of SERBP1, generated by alternative mRNA splicing, interacted with RACK1 with indistinguishable interaction strength, as determined by a 2-hybrid beta-galactosidase assay. Analysis of deletion constructs of SERBP1 showed that the C-terminal third of the SERBP1 protein, which contains one of its two substrate sites for protein arginine N-methyltransferase 1 (PRMT1), is necessary and sufficient for it to interact with RACK1. Analysis of single amino acid substitutions in RACK1, identified in a reverse 2-hybrid screen, showed very substantial overlap with those implicated in the interaction of RACK1 with the cAMP-selective phosphodiesterase PDE4D5. These data are consistent with SERBP1 interacting selectively with RACK1, mediated by an extensive interaction surface on both proteins.

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Posttranscriptional regulation of expression of plasminogen activator inhibitor type-1 by sphingosine 1-phosphate in HepG2 liver cells

Cited by 13 publications

References 39 publications

SERBP1 Is a Component of the Liver Receptor Homologue-1 Transcriptional Complex

SERBP1 Is a Component of the Liver Receptor Homologue-1 Transcriptional Complex

Sphingosine 1-phosphate induced by hypoxia increases the expression of PAI-1 in HepG2 cells via HIF-1α

The RNA-binding protein SERBP1 interacts selectively with the signaling protein RACK1

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