25-hydroxycholesterol down-regulates oxysterol binding protein like 2 (OSBPL2) via the p53/SREBF2/NFYA signaling pathway

Wang, Quan; Lin, Changsong; Zhang, Cui; Wang, Hongshun; Lu, Yajie; Yao, Jun; Wei, Qinjun; Xing, Guangqian; Cao, Xin

doi:10.1016/j.jsbmb.2018.10.018

Cited by 7 publications

(9 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the viability of cells was not affected by any of treatments. The dosage of oxysterols in the present study was also within the normal dosage compare to previous published studies [41,42]. However, it is worthy to test an apoptosis possibility as an inhibition mechanism of 25-HC in a future study…”

Section: Discussionsupporting

confidence: 71%

25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells

Moseti

Regassa

Chen

et al. 2020

IJMS

View full text Add to dashboard Cite

Oxysterols have been shown to inhibit adipogenic differentiation of mesenchymal stem cells while inducing their osteogenic differentiation. However, the effects of oxysterols on the adipogenic differentiation of C3H10T1/2 mouse stem cells are poorly understood. This study was conducted to examine the effects of specific oxysterols on the expression of adipogenic transcripts and adipogenic differentiation of C3H10T1/2 mouse stem cells. Cells were treated with 10% Fetal Bovine Serum (control), 500nM Dexamethasone, 0.5mM 3‐Isobutyl‐1‐methlyxanthine, 20µg/ml Insulin (DMI) + 10µM PPARγ agonist Troglitazone (Tro) (DMITro) and DMITro + 10µM 20S hydroxycholesterol (20S), 25 hydroxycholesterol (25), 22R hydroxycholesterol (22R) or 22S hydroxycholesterol (22S) for six days. Gene expression was analysed by real‐time quantitative polymerase chain reaction and expression data analysed using the Statistical Analysis Software (SAS 9.2). Compared to the control, DMITro significantly increased the expression of peroxisome proliferator‐activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid binding protein 2 (FABP2) and lipoprotein lipase (LPL). Compared to DMITro, treatment of cells with DMITro + 25 significantly decreased the expression of PPARγ, the master regulator of adipogenesis (P 蠄 0.05). Expression of C/EBPα was significantly decreased by DMITro + 25 and DMITro + 20S (P 蠄 0.05), while the expression of FABP2 was significantly decreased by DMITro + 25, DMITro + 20S and DMITro + 22R (P 蠄 0.05). Lastly, the expression of LPL was significantly decreased by DMITro + 25 and DMITro + 22R (P 蠄 0.05). In conclusion, the results showed that 25 hydroxycholesterol was the most potent in inhibiting the expression of key adipogenic transcripts and adipogenesis of C3H10T1/2 mouse stem cells suggesting its potential application in reducing adipogenesis and obesity. Key words: Oxysterols, C3H10T1/2 stem cells, differentiation, PPARγ Grant Funding Source: Supported by Canadian natural science and engineering research council.

show abstract

Section: Discussionsupporting

confidence: 71%

25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells

Moseti

Regassa

Chen

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Finally, expression of PHF20 which is associated with the p53 signal pathway has not been reported in CRC, but might be associated with its development. We suggest that four specific genotypes, including DDX27 /CN gain, MAPRE1 /CN gain, OSBPL2 /CN gain and PHF20 /CN gain, may be major molecular events in the progression to CRC 43 …”

Section: Discussionmentioning

confidence: 94%

“…In addition, high expression of OSBPL2 was associated with a gain at this gene locus. OSBPL2 is associated with the p53/SREBF2/NFYA signal pathway 43 . OSBPL2 might be induced via this pathway and serve as a cancer‐induced molecule.…”

Section: Discussionmentioning

confidence: 99%

A genome‐wide study of the relationship between chromosomal abnormalities and gene expression in colorectal tumors

Sugai

Osakabe

Sugimoto

et al. 2020

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

The role of somatic copy number alterations (SCNAs) that occur in colorectal tumors is poorly understood. SCNAs are correlated with corresponding gene expression changes that may contribute to neoplastic progression. Thus, we examined SCNAs and the expression of messenger RNAs (mRNAs) located at corresponding loci in colorectal neoplasia, a progression model of human neoplasm. We used 42 colorectal neoplastic samples, including adenomas, intramucosal cancers (IMC) and invasive colorectal cancers (CRC) that were microsatellite stable (MSS) using a genome‐wide SNP array and gene expression array (first cohort). In addition, validation analyses were examined (37 colorectal neoplasias). None of the mRNAs with a corresponding SCNA was found in the adenomas. However, three mRNAs, including ARFGEF2 at 20q13.13, N4BP2L2 at 13q13.1 and OLFM4 at 13q14.3 with a copy number (CN) gain at the corresponding locus were upregulated in IMCs of the first cohort. Moreover, upregulated expression of ARFGEF2 and OLFM4 was upregulated in the validation analysis. Finally, 28 mRNAs with gains of corresponding loci were pooled in invasive CRC of the first cohort. The mRNAs, including ACSS2 (20q11.22), DDX27 (20q13.13), MAPRE1 (20q11.21), OSBPL2 (20q11.22) and PHF20 (20q11.22‐q11.23) with CN gains of the corresponding loci were identified in 28 mRNAs. Four of these mRNAs (DDX27, MAPRE1, OSBPL2 and PHF20) were upregulated in the invasive CRC in the validation analysis. We conclude that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.

show abstract

“…Especially in the OSBPL2 -disrupted pigs, we reproduced not only a deafness phenotype similar to that of humans but also a hypercholesterolemia phenotype ( Yao et al., 2019 ). In subsequent studies of OSBPL2/ORP2 functions, we found that OSBPL2 was downregulated by 25-hydroxycholesterol ( Wang et al., 2019c ). In OC1 cells, the deletion of OSBPL2 led to increased cholesterol biosynthesis and upregulated ROS production ( Wang et al., 2019a ).…”

Section: Discussionmentioning

confidence: 99%

OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Summary The accumulation of giant lipid droplets (LDs) increases the risk of metabolic disorders including obesity and insulin resistance. The lipolysis process involves the activation and transfer of lipase, but the molecular mechanism is not completely understood. The translocation of ATGL, a critical lipolysis lipase, from the ER to the LD surface is mediated by an energy catabolism complex. Oxysterol-binding protein-like 2 (OSBPL2/ORP2) is one of the lipid transfer proteins that regulates intracellular cholesterol homeostasis. A recent study has proven that Osbpl2 −/− pigs exhibit hypercholesterolemia and obesity phenotypes with an increase in adipocytes. In this study, we identified that OSBPL2 links the endoplasmic reticulum (ER) with LDs, binds to COPB1, and mediates ATGL transport. We provide important insights into the function of OSBPL2, indicating that it is required for the regulation of lipid droplet lipolysis.

show abstract

25-hydroxycholesterol down-regulates oxysterol binding protein like 2 (OSBPL2) via the p53/SREBF2/NFYA signaling pathway

Cited by 7 publications

References 33 publications

25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells

25-Hydroxycholesterol Inhibits Adipogenic Differentiation of C3H10T1/2 Pluripotent Stromal Cells

A genome‐wide study of the relationship between chromosomal abnormalities and gene expression in colorectal tumors

OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis

Contact Info

Product

Resources

About