發(fā)布時(shí)間：2018-04-24 19:41

  本文選題：血清淀粉樣蛋白A + Jmjd3��； 參考：《上海交通大學(xué)》2014年碩士論文

【摘要】：血清淀粉樣蛋白A，作為一種急性期反應(yīng)蛋白，在吞噬細(xì)胞和滑膜成纖維細(xì)胞中具有與細(xì)胞因子類似的作用。盡管轉(zhuǎn)錄因子如NF-B的活化對(duì)SAA誘導(dǎo)促炎基因表達(dá)具有重要作用，但在這一過程中，表觀遺傳學(xué)調(diào)控機(jī)制仍不清楚。本課題研究發(fā)現(xiàn)，在SAA刺激后的小鼠骨髓巨噬細(xì)胞、腹膜巨噬細(xì)胞和小鼠巨噬細(xì)胞系RAW264.7中，組蛋白H3K27去甲基化酶Jmjd3顯著上調(diào)。同時(shí)，SAA誘導(dǎo)Jmjd3表達(dá)伴隨著細(xì)胞內(nèi)組蛋白H3K27me3表達(dá)水平的下調(diào)。在小鼠巨噬細(xì)胞系RAW264.7中，當(dāng)Jmjd3基因被沉默或過表達(dá)無活性的Jmjd3突變蛋白時(shí)，SAA誘導(dǎo)促炎基因如IL-23p19, G-CSF, TREM-1等表達(dá)過程受到明顯抑制，并伴隨著啟動(dòng)子區(qū)H3K27me3甲基化水平的上調(diào)。此外，小鼠體內(nèi)實(shí)驗(yàn)進(jìn)一步證明Jmjd3基因沉默可抑制SAA誘導(dǎo)腹腔巨噬細(xì)胞促炎基因的表達(dá)，并下調(diào)由SAA引起的中性粒細(xì)胞增多。最后，我們還發(fā)現(xiàn)Jmjd3在SAA誘導(dǎo)的巨噬細(xì)胞泡沫化形成中起到重要作用�？傊�，本課題闡明了一條依賴于Jmjd3調(diào)控的SAA誘導(dǎo)促炎細(xì)胞因子表達(dá)的信號(hào)通路，，并為治療無菌炎癥和動(dòng)脈粥樣硬化癥指明了潛在的藥物靶點(diǎn)。
[Abstract]:Serum amyloid A, as an acute phase reactive protein, plays a similar role with cytokines in phagocytes and synovial fibroblasts. Although the activation of transcription factors such as NF-B plays an important role in the expression of pro-inflammatory genes induced by SAA, the epigenetic regulation mechanism remains unclear. In this study, we found that histone H3K27 demethylase Jmjd3 was significantly up-regulated in SAA stimulated mouse bone marrow macrophages, peritoneal macrophages and mouse macrophages RAW264.7. At the same time, the expression of Jmjd3 was accompanied by down-regulation of histone H3K27me3 expression. In murine macrophage cell line RAW264.7, when the Jmjd3 gene is silenced or overexpression of inactive Jmjd3 mutant protein, the expression process of proinflammatory genes such as IL-23p19, G-CSF, TREM-1 is significantly inhibited, accompanied by the up-regulation of H3K27me3 methylation in the promoter region. In addition, Jmjd3 gene silencing could inhibit the expression of pro-inflammatory gene in peritoneal macrophages induced by SAA and down-regulate the increase of neutrophil induced by SAA in mice. Finally, we found that Jmjd3 plays an important role in the formation of macrophage foam induced by SAA. In conclusion, this study elucidates a signal pathway of pro-inflammatory cytokine expression induced by SAA, which is dependent on the regulation of Jmjd3, and identifies potential drug targets for the treatment of aseptic inflammation and atherosclerosis.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R965

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 張廣俠;李濤;;神經(jīng)系統(tǒng)中組蛋白修飾調(diào)控的研究進(jìn)展[J];廣東醫(yī)學(xué);2013年02期

2 Danila Coradini;Saro Oriana;;The role of maintenance proteins in the preservation of epithelial cell identity during mammary gland remodeling and breast cancer initiation[J];Chinese Journal of Cancer;2014年02期

3 Sheng-Wei Ren;Xia Qi;Chang-Kai Jia;Yi-Qiang Wang;;Serum amyloid A and pairing formyl peptide receptor 2 are expressed in corneas and involved in inflammation-mediated neovascularization[J];International Journal of Ophthalmology(English Edition);2014年02期

4 江青山;鄧珊;沈?qū)氒?;SAA對(duì)鼻咽癌CNE2細(xì)胞生物學(xué)行為的影響[J];重慶醫(yī)學(xué);2015年06期

5 Juan Xu;Bo Yu;Christine Hong;Cun-Yu Wang;;KDM6B epigenetically regulates odontogenic differentiation of dental mesenchymal stem cells[J];International Journal of Oral Science;2013年04期

6 黃瑞良;林偉文;阮藝;熊浩;劉偉;夏雄超;凌華軍;;紅細(xì)胞沉降率、C反應(yīng)蛋白及血清淀粉樣蛋白在不同類型人工髖關(guān)節(jié)置換術(shù)前后的變化及臨床意義研究[J];華西醫(yī)學(xué);2014年07期

7 楊學(xué);馮喜英;張Z

本文編號(hào)：1797956