scholarly journals Intestinal maturation in mice lacking CCAAT/enhancer-binding protein α (C/EPBα)

1998 ◽  
Vol 330 (3) ◽  
pp. 1165-1171 ◽  
Author(s):  
J. Thomas OESTERREICHER ◽  
L. Lucy LEEPER ◽  
J. Milton FINEGOLD ◽  
J. Gretchen DARLINGTON ◽  
J. Susan HENNING
Keyword(s):  
Glucose Transporter ◽  
Binding Protein ◽  
Fatty Acid Binding Proteins ◽  
Mrna Levels ◽  
Fatty Acid Binding ◽  
Proliferative Zone ◽  
Glucose Transporter 2 ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Morphological Maturation

In rodents, there is a surge of intestinal expression of CCAAT/enhancer-binding protein α (C/EBPα) in the late fetal phase just before morphological maturation and the onset of expression of numerous epithelial genes. To investigate directly the hypothesis that C/EBPα plays a causal role in the latter phenomena, we have assessed both structural and functional maturation in neonatal intestine from C/EBPα-null mice and their littermates. No effects of C/EBPα genotype were observed on mucosal architecture or on the size of the proliferative zone in the intestinal crypts. Likewise, the mRNA levels for the glucose transporter 2 (GLUT2), intestinal and liver fatty acid-binding proteins, and apolipoprotein A-IV in newborn intestine were similar in all genotypes. Paradoxically, Na+/glucose co-transporter (SGLT1), lactase phlorizin-hydrolase and apolipoprotein B mRNAs were more abundant in the C/EBPα-deficient animals. In wild-type intestines, C/EBPβ and C/EBPΔ mRNAs were detectable throughout the late fetal period and increased toward term in parallel with C/EBPα mRNA. In newborn intestine, there was no compensatory up-regulation of these isoforms in the C/EBPα-deficient mice. We conclude that C/EBPα has no essential role in morphological maturation of the intestine, the pattern of proliferation of the epithelium, or the onset of expression of this cluster of epithelial mRNAs. However, since other C/EBP isoforms are present in the developing intestine, it is possible that there is a generic requirement for a member of the C/EBP family.

Overexpression of CCAAT Enhancer-Binding Protein α Inhibits the Growth of K562 Cells via the Foxo3a-Bim Pathway

2016 ◽  
Vol 136 (2) ◽  
pp. 65-70 ◽  
Author(s):  
Guili Zhang ◽  
Fei Dong ◽  
Caifu Luan ◽  
Xia Zhang ◽  
Huiyuan Shao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Binding Protein ◽  
K562 Cells ◽  
Cell Counting ◽  
Stable Cell Line ◽  
Mrna Levels ◽  
Forkhead Transcription Factor ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Blood Specimens

We aimed to investigate the role of CCAAT enhancer-binding protein α (C/EBPα) in the pathogenesis of chronic myeloid leukemia (CML) and the mechanism underlying its effect. Bone marrow specimens from 50 patients with CML and peripheral blood specimens from 20 healthy individuals were collected. K562 cells were treated with imatinib. Subsequently, a stable cell line, K562-C/EBPα, was constructed. Cell proliferation was assayed with cell counting kit-8, and mRNA levels of C/EBPα, forkhead transcription factor FKHRL1 (Foxo3a) and Bim were detected by semiquantitative PCR. The correlation of C/EBPα and BCR-ABL was assessed by Spearman's correlation analysis. The results showed that C/EBPα mRNA levels were significantly reduced in CML patients compared with healthy subjects (p < 0.001) and were negatively correlated with BCR-ABL1 (r = -0.5046, p < 0.01). Additionally, imatinib enhanced the expression of C/EBPα in K562 cells compared with untreated cells (p < 0.05). Overexpression of C/EBPα significantly decreased cell proliferation and upregulated the expressions of the apoptosis-related genes Foxo3a (p < 0.01) and Bim (p < 0.05) in K562 cells. In conclusion, C/EBPα expression was decreased in patients with CML. Imatinib enhances the expression of C/EBPα in K562 cells, and the overexpression of C/EBPα inhibits cell proliferation and increases apoptosis via the Foxo3a-Bim pathway.

scholarly journals Restoration of adipose function in obese glucose-tolerant men following pioglitazone treatment is associated with CCAAT enhancer-binding protein β up-regulation

2012 ◽  
Vol 123 (3) ◽  
pp. 135-146 ◽  
Author(s):  
Lesley A. Powell ◽  
Paul Crowe ◽  
Chenchi Kankara ◽  
Jennifer McPeake ◽  
David R. McCance ◽  
...  
Keyword(s):  
Cell Surface ◽  
Glucose Transporter ◽  
Binding Protein ◽  
Regulatory Element ◽  
Controlled Trial ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Glucose Tolerant ◽  
Adipocyte Cell ◽  
Pioglitazone Treatment

Obese AT (adipose tissue) exhibits increased macrophage number. Pro-inflammatory CD16+ peripheral monocyte numbers are also reported to increase with obesity. The present study was undertaken to simultaneously investigate obesity-associated changes in CD16+ monocytes and ATMs (AT macrophages). In addition, a pilot randomized placebo controlled trial using the PPAR (peroxisome-proliferator-activated receptor) agonists, pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16+ monocytes, ATM and cardiometabolic and adipose dysfunction indices. Obese glucose-tolerant men (n=28) were randomized to placebo, pioglitazone (30 mg/day) and fenofibrate (160 mg/day) for 12 weeks. A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16+ monocyte levels via flow cytometry. A subcutaneous AT biopsy was performed to determine adipocyte cell surface and ATM number, the latter was determined via assessment of CD68 expression by IHC (immunohistochemistry) and real-time PCR. Subcutaneous AT mRNA expression of CEBPβ (CCAAT enhancer-binding protein β), SREBP1c (sterol-regulatory-element-binding protein 1c), PPARγ2, IRS-1 (insulin receptor substrate-1), GLUT4 (glucose transporter type 4) and TNFα (tumour necrosis factor α) were also assessed. Comparisons were made between obese and lean controls (n=16) at baseline, and pre- and post-PPAR agonist treatment. Obese individuals had significantly increased adipocyte cell surface, percentage CD14+/CD16+ monocyte numbers and ATM number (all P=0.0001). Additionally, serum TNF-α levels were significantly elevated (P=0.017) and adiponectin levels reduced (total: P=0.0001; high: P=0.022) with obesity. ATM number and percentage of CD14+/CD16+ monocytes correlated significantly (P=0.05). Pioglitazone improved adiponectin levels significantly (P=0.0001), and resulted in the further significant enlargement of adipocytes (P=0.05), without effect on the percentage CD14+/CD16+ or ATM number. Pioglitazone treatment also significantly increased subcutaneous AT expression of CEBPβ mRNA. The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels, supports the centrality of AT to the cardiometabolic derangement underlying the development of T2D (Type 2 diabetes) and CVD (cardiovascular disease).

Exchange protein directly activated by cAMP (EPAC) promotes transcriptional activation of the decidual prolactin gene via CCAAT/enhancer-binding protein in human endometrial stromal cells

2018 ◽  
Vol 30 (11) ◽  
pp. 1454
Author(s):  
Kazuya Kusama ◽  
Kazuhiro Tamura ◽  
Hanako Bai ◽  
Toshihiro Sakurai ◽  
Hirotaka Nishi ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Binding Protein ◽  
Luciferase Assay ◽  
Mrna Levels ◽  
Reporter Activity ◽  
Camp Analogue ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Decidual Prolactin ◽  
Exchange Protein

Protein kinase A (PKA) signalling accompanies elevated intracellular cAMP levels during endometrial stromal cell (ESC) decidualisation. Exchange protein directly activated by cAMP (EPAC), an alternate mediator of cAMP signalling, promotes PKA analogue-induced decidualisation; however, the precise mechanism by which EPAC and PKA co-operatively stimulate decidualisation has not been characterised. To examine the role of CCAAT/enhancer-binding protein (C/EBP) in EPAC- and PKA-mediated decidualisation of primary human ESCs, a reporter plasmid containing the 332 bp region upstream from the transcription initiation site of the decidual prolactin (dPRL) gene was generated and the promoter activity was evaluated using a luciferase assay. The dPRL promoter activity was increased by treatment of transfected ESCs with the PKA-selective cAMP analogue N6-phenyl-cAMP (Phe) and enhanced further by co-treatment with the EPAC-selective cAMP analogue 8-(4-chlorophenyltio)-2′-O-methyl cAMP (CPT). Treatment with forskolin, an adenylyl cyclase activator, had a similar effect on reporter activity. Site-directed mutagenesis of the C/EBPβ- and/or C/EBPδ-binding site in the dPRL promoter abolished Phe/CPT-mediated elevation of the reporter activity. EPAC2 knockdown markedly reduced Phe-stimulated C/EBPβ and C/EBPδ mRNA levels, as well as forkhead box O1 (FOXO1) protein levels. These results suggest that EPAC signalling enhances PKA-mediated dPRL expression in ESCs by acting on C/EBP response elements in the promoter region of the gene.

scholarly journals Knockdown of LXRα Inhibits Goat Intramuscular Preadipocyte Differentiation

2018 ◽  
Vol 19 (10) ◽  
pp. 3037 ◽  
Author(s):  
Yan Xiong ◽  
Qing Xu ◽  
Sen Lin ◽  
Yong Wang ◽  
Yaqiu Lin ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Early Stage ◽  
Binding Protein ◽  
Regulatory Element ◽  
Adipogenic Differentiation ◽  
Mrna Level ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

Goat intramuscular fat (IMF) content is mainly determined by the processes of intramuscular preadipocytes adipogenic differentiation and mature adipocyte lipid accumulation. However, the underlying regulators of these biological processes remain largely unknown. Here, we report that the expression of Liver X receptor alpha (LXRα) reaches a peak at early stage and then gradually decreases during goat intramuscular adipogenesis. Knockdown of LXRα mediated by two independent siRNAs significantly inhibits intramuscular adipocytes lipid accumulation and upregulates preadipocytes marker- preadipocyte factor 1 (pref1) expression. Consistently, siRNA treatments robustly decrease mRNA level of adipogenic related genes, including CCAAT enhancer binding protein alpha (Cebpα), Peroxisome proliferator activated receptor gamma (Pparg), Sterol regulatory element binding protein isoform 1c (Srebp1c), Fatty acids binding protein (aP2) and Lipoprotein lipase (Lpl). Next, adenovirus overexpression of LXRα does not affect intramuscular adipocytes adipogenesis manifested by Oil Red O signal measurement and adipogenic specific genes detection. Mechanically, we found that both CCAAT enhancer binding protein beta (Cebpβ) and Kruppel like factor 8 (Klf8) are potential targets of LXRα, indicated by having putative binding sites of LXRα at the promoter of these genes and similar expression pattern during adipogenesis comparing to LXRα. Importantly, mRNA levels of Cebpβ and Klf8 are downregulated significantly in goat LXRα knockdown intramuscular adipocyte. These results demonstrate that loss function of LXRα inhibits intramuscular adipogenesis possibly through down-regulation of Cebpβ and Klf8. Our research will provide new insights into mechanical regulation of goat IMF deposition.

C/EBPβ (CCAAT/Enhancer Binding Protein) Controls Cell Fate Determination during Mammary Gland Development

2000 ◽  
Vol 14 (3) ◽  
pp. 359-368 ◽  
Author(s):  
Tiffany N. Seagroves ◽  
John P. Lydon ◽  
Russell C. Hovey ◽  
Barbara K. Vonderhaar ◽  
Jeffrey M. Rosen
Keyword(s):  
Mammary Gland ◽  
Cell Fate ◽  
Binding Protein ◽  
Mammary Glands ◽  
Mammary Development ◽  
Mrna Levels ◽  
Wild Type ◽  
Cell Fate Decisions ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

Abstract Deletion of the transcription factor CCAAT/enhancer binding protein (C/EBP)β results in a severe inhibition of lobuloalveolar development in the mouse mammary gland. Because progesterone receptor (PR) is requisite for alveolar development, the expression of PR was investigated in C/EBPβ−/− mice. Unexpectedly, the number of PR-positive cells, as well as the levels of PR mRNA, were elevated 3-fold in the mammary glands of C/EBPβ−/− mice. Furthermore, in contrast to wild-type nulliparous mice, in which PR distribution shifted from a uniform to nonuniform pattern between 8–12 weeks of age, C/EBPβ−/− mice exhibited uniform PR distribution throughout all stages of mammary development analyzed. No change in C/EBPβ mRNA levels was observed in the mammary glands of PR−/− mice, suggesting that PR acts in a pathway either in parallel to or downstream of C/EBPβ. The overexpression and disrupted cellular distribution of PR in C/EBPβ−/− mice were coincident with a striking 10-fold decrease in cell proliferation after acute steroid hormone treatment, assayed by incorporation of bromodeoxyuridine. In wild-type mice, PR and bromodeoxyuridine-positive cells were adjacent to each other and rarely colocalized. No differences in the level or pattern of PR expression were observed in the uterus, suggesting that C/EBPβ influences PR in a mam-mary-specific fashion. Together, these data suggest that C/EBPβ may control cell fate decisions in the mammary gland through the appropriate temporal and spatial expression of molecular markers, such as PR, that induce the proliferation of alveolar progenitor cells via juxtacrine mechanisms.

The CCAAT/enhancer-binding protein-alpha is expressed in the germinal layer of the growth plate: colocalisation with the growth hormone receptor

1997 ◽  
Vol 155 (3) ◽  
pp. 433-441 ◽  
Author(s):  
NO Vidal ◽  
S Ekberg ◽  
S Enerback ◽  
A Lindahl ◽  
C Ohlsson
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Binding Protein ◽  
Mrna Levels ◽  
Germinal Layer ◽  
Gh Receptor ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Rat Growth ◽  
Factor C

The transcription factor C/EBP alpha, a member of the CCAAT/enhancer-binding protein family, is highly expressed in the liver and in adipose tissue. The aim of this study was to determine if C/EBP alpha is expressed in rat growth cartilage. The expression pattern of C/EBP alpha in monolayer-cultured growth plate chondrocytes was similar to that of C/EBP alpha during hepatocyte and preadipocyte differentiation. Immunohistochemistry with a polyclonal antibody for C/EBP alpha revealed that the C/EBP alpha protein is present in the perichondrial ring, in the germinal layer of the growth plate and on the surface of the articular cartilage. The growth hormone (GH) receptor has a similar distribution in the rat tibial growth plate, and hypophysectomised rats were used to investigate a possible connection between C/EBP alpha and GH. C/EBP alpha mRNA levels were decreased in rib cartilage after hypophysectomy. However, GH treatment did not counteract this effect, indicating that other pituitary hormones regulate the C/EBP alpha mRNA levels in growth plate cartilage. We thus demonstrate, for the first time, that C/EBP alpha is expressed in cartilage. The finding that C/EBP alpha, like the GH receptor, is predominantly expressed in stem cell areas of the rat growth plate indicates a possible functional role for C/EBP alpha during early chondrogenic differentiation.

scholarly journals SF-1 (Steroidogenic Factor-1) and C/EBPβ (CCAAT/Enhancer Binding Protein-β) Cooperate to Regulate the Murine StAR (Steroidogenic Acute Regulatory) Promoter

1999 ◽  
Vol 13 (5) ◽  
pp. 729-741 ◽  
Author(s):  
Adam J. Reinhart ◽  
Simon C. Williams ◽  
Barbara J. Clark ◽  
Douglas M. Stocco
Keyword(s):  
Binding Sites ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Mrna Levels ◽  
Inner Mitochondrial Membrane ◽  
Mobility Shift ◽  
Steroidogenic Factor 1 ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Steroidogenic Acute Regulatory

Abstract The steroidogenic acute regulatory (StAR) protein mediates the rate-limiting step of steroidogenesis, which is the transfer of cholesterol to the inner mitochondrial membrane. In steroidogenic tissues, StAR expression is acutely regulated by trophic hormones through a cAMP second messenger pathway, leading to increased StAR mRNA levels within 30 min, reaching maximal levels after 4–6 h of stimulation. The molecular mechanisms underlying such regulation remain unknown. We have examined the StAR promoter for putative transcription factor-binding sites that may regulate transcription in a developmental and/or hormone-induced context. Through sequence analysis, deoxyribonuclease I (DNAse I) footprinting and electrophoretic mobility shift assays (EMSAs), we have identified two putative CCAAT/enhancer binding protein (C/EBP) DNA elements at −113 (C1) and −87 (C2) in the mouse StAR promoter. Characterization of these sites by EMSA indicated that C/EBPβ bound with high affinity to C1 and C2 was a low-affinity C/EBP site. Functional analysis of these sites in the murine StAR promoter showed that mutation of one or both of these binding sites decreases both basal and (Bu)2cAMP-stimulated StAR promoter activity in MA-10 Leydig tumor cells, without affecting the fold activation[ (Bu)2cAMP-stimulated/basal] of the promoter. Furthermore, we have demonstrated that these two C/EBP binding sites are required for steroidogenic factor-1 (SF-1)-dependent transactivation of the StAR promoter in a nonsteroidogenic cell line. These data indicate that in addition to SF-1, C/EBPβ is involved in the transcriptional regulation of the StAR gene and may play an important role in developmental and hormone-responsive regulation of steroidogenesis.

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