作者: Zhuyi Li ; Ming Yu ; Zhe Wang ; Lijun Zhang ; Zengshan Li ; Peizhen Hu ; Feng Zhang ; Jing Ye ; Yingmei Wang ; Xing Gao ; Chao Sun ; Kaiyu Cao ; Sheng Li ; Bingcheng Ren ; Yuan Yuan ; Chao Wang ; Jiankuan Shi ; Weihua Liang ; Yuanlin Zhao ; Yu Gu

BACKGROUNDAbnormal lipid metabolism is one of many factors that contribute to the development of ulcerative colitis (UC). As a lipid droplet-associated protein, Cideb facilitated the export of lipids from enterocytes and promoted intestinal lipid absorption. We found that Cideb was upregulated in the colonic mucosa of both UC patients and dextran sodium sulfate (DSS)-induced mouse colitis, but its roles in the pathogenesis of UC are still ill-defined.METHODSAcute colitis was induced with DSS in Cideb-null and wild-type mice, and the inflammation and oxidative stress were evaluated in the colonic mucosa. Moreover, triglyceride accumulation and oxidative stress were further analyzed in polarized Caco-2 cells with overexpression of Cideb.RESULTSOur present data indicated that Cideb-null mice were more susceptible to DSS-induced colitis, and consumption of a high-fat diet exacerbated the deterioration of DSS-induced colitis in Cideb-null mice. Moreover, Cideb deficiency increased the colonic oxidative stress in DSS-treated mice and more significant under a high-fat diet condition. In exploring the mechanism, we found that Cideb deficiency elevated the lipid content in both feces and the colonic mucosa of DSS-treated mice, especially those fed with a high-fat diet. The in vitro evidence proved that Cideb expression reduced triglyceride accumulation and oxidative stress in polarized Caco-2 cells in the presence of oleic acid.CONCLUSIONSOur data suggest that Cideb plays a protective role against the development of UC by reducing the lipid accumulation and oxidative damage in the colonic mucosa. Therefore, Cideb could be a potential therapeutic target for UC.

2012-02-01·Diabetes/Metabolism Research and Reviews3区 · 医学

Cell death‐inducing DFF45‐like effector b (Cideb) is present in pancreatic beta‐cells and involved in palmitate induced beta‐cell apoptosis

3区 · 医学

Article

作者: Li, H. ; Ye, J. ; Jiang, L. N. ; Zhang, L. Y. ; Song, Y. ; Li, F. F. ; Wang, J. ; Gu, Y. ; Zhang, J. ; Liu, F. ; Dong, W. P. ; Zhang, L. J. ; Li, Q. ; Xue, L.

AbstractBackgroundExcessive accumulation of long‐chain fatty acids in the pancreatic islets is associated with beta cell dysfunction and ultimately contributes to the pathogenesis of type 2 diabetes. It has been well proved that the cell death‐inducing DFF45‐like effector b (Cideb) is involved in cell apoptosis and lipid metabolism. However, the expression and function of Cideb in endocrine pancreas remain to be investigated.MethodsBy using reverse transcript polymerase chain reaction, immunohistochemistry and Western blot, we observed the expression of Cideb in pancreas tissues and clonal beta‐cell lines. The physiological role of Cideb was examined under the free fatty acid (FFA) administration and Cideb ribonucleic acid interference, and further analysis on apoptosis was measured by terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling assay and caspase‐3 activity. Nile red staining and quantitative evaluation of triglyceride were used to detect the lipid accumulation. The changes in esterification of FFA were traced by radiolabelled palmitate.ResultsCideb was abundantly expressed in pancreas and mainly localized in beta cells. FFAs, especially palmitate, induced an obvious increase of Cideb expression in beta cell lines. Adenoviral‐mediated overexpression of Cideb increased the apoptosis, whereas ribonucleic acid interference‐based Cideb depletion in beta‐TC3 cells had no effect on apoptosis in normal condition. Palmitate supplementation led to beta cell lipoapoptosis, and Cideb silencing exacerbated the apoptosis induced by palmitate, reduced intracellular triglyceride content and aggravated FFA overload in beta cells.ConclusionsThe present results suggest that increased Cideb expression upon palmitate exposure may be involved in beta cell lipoapoptosis through its influence on conversion of FFAs to lipid esters in lipid droplets. Copyright © 2011 John Wiley & Sons, Ltd.

2006-02-01·Biochemical Journal3区 · 生物学

Dual promoters control the cell-specific expression of the human cell death-inducing DFF45-like effector B gene

3区 · 生物学

Article

作者: Li, Tsaiping ; Zhao, Mujun ; Li, Dong ; Yokoyama, Kazunari K. ; Da, Liang

CIDE-B [cell death-inducing DFF45 (DNA fragmentation factor 45)-like effector B] is a member of the CIDE family of apoptosis-inducing factors. The highly restricted pattern of expression of CIDE-B in the liver and spleen suggests that a mechanism exists for the tissue- and cell-specific regulation of transcription of this gene. We have analysed the promoters of the human CIDE-B gene, particularly the mechanism of cell-specific transcription. Expression of CIDE-B is driven by two promoters which are responsible for the synthesis of two types of transcript, and Sp1 and Sp3 are key regulators of basal transcription from both the upstream and the internal promoter, as indicated by EMSAs (electrophoretic mobility-shift assays) and site-directed mutagenesis. Bisulphite sequencing analysis demonstrated that the upstream promoter was hypermethylated in cells that did not express the long transcript of CIDE-B, but was hypomethylated in cells that expressed this transcript. Furthermore, methylation of this region in vitro reduced the promoter activity to ∼5% of the control. Thus methylation at CpG sites in the upstream promoter region appeared to be important for cell-specific synthesis of the long transcript. By contrast, HNF4α (hepatocyte nuclear factor-4α) bound to the internal promoter and enhanced its activity. Moreover, the short transcript of CIDE-B gene was expressed in cells which do not normally express this transcript upon introduction of exogenous HNF4α, demonstrating the involvement of HNF4α in the cell-specific synthesis of the short transcript. Thus our analysis revealed a novel mechanism for the cell-specific transcription of the human CIDE-B gene, which involves epigenetic and genetic control at separate respective promoters.

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适应症	最高研发状态	国家/地区	公司	日期
非酒精性脂肪性肝炎	临床前	美国	Regeneron Pharmaceuticals, Inc.	2022-07-27
非酒精性脂肪性肝炎	临床前	美国	Alnylam Pharmaceuticals, Inc.	2022-07-27