促红细胞生成素通过激活ERK和p38 MAPK抑制小鼠骨髓间充质干细胞成脂分化

发布时间：2018-01-01 11:24

本文关键词：促红细胞生成素通过激活ERK和p38 MAPK抑制小鼠骨髓间充质干细胞成脂分化　出处：《中国病理生理杂志》2013年11期 　论文类型：期刊论文

【摘要】：目的:探讨促红细胞生成素(EPO)是否抑制小鼠骨髓间充质干细胞(MSCs)分化为脂肪细胞及其机制。方法:分离提取小鼠骨髓MSCs,用3-异丁基-1-甲基黄嘌呤、胰岛素和地塞米松联合诱导成脂分化,实验组加入不同浓度EPO干预,诱导分化第20天油红O染色观察并进行定量分析细胞分化程度;MTT法观察不同浓度EPO对MSCs增殖能力的影响。实时荧光定量PCR检测过氧化物酶体增殖物激活受体γ(PPARγ)、CCAAT/增强子结合蛋白α(C/EBPα)、脂肪酸结合蛋白4(FABP4)和脂联素mRNA表达水平;Western blotting检测PPARγ及细胞外信号调节激酶(ERK)和p38丝裂原活化蛋白激酶(p38 MAPK)磷酸化水平。结果:诱导分化20 d,EPO能显著抑制MSCs的成脂分化,降低油红O染色后的吸光度值,诱导分化过程中各浓度的EPO不影响MSCs增殖活性。EPO能够下调成脂过程中PPARγ、C/EBPα、FABP4和脂联素mRNA表达,增加分化过程中ERK、p38 MAPK及PPARγ蛋白磷酸化。结论:EPO可能通过增加p38 MAPK和ERK蛋白磷酸化,下调PPARγ、C/EBPα、FABP4和脂联素mRNA表达,从而抑制MSCs成脂分化。
[Abstract]:Objective: to investigate whether erythropoietin (EPO) inhibits the differentiation of murine bone marrow mesenchymal stem cells (MSCs) into adipocytes and its mechanism. Methods: mouse bone marrow MSCs was isolated and extracted. Lipid differentiation was induced by 3-isobutyl -1-methylxanthine, insulin and dexamethasone. The experimental group was treated with different concentrations of EPO. On the 20th day after induction, the degree of differentiation was observed and quantitatively analyzed by oil red O staining. The effects of different concentrations of EPO on the proliferation of MSCs were observed by MTT method. The peroxisome proliferator activated receptor 纬 (PPAR- 纬) was detected by real-time quantitative PCR. The expression levels of CCAAT- / enhancer binding protein 伪 C / EBP 伪, fatty acid binding protein 4 (FABP4) and adiponectin mRNA; Western blotting detection of PPAR 纬, extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK). Results: differentiation was induced for 20 days. EPO could significantly inhibit the adipogenic differentiation of MSCs and decrease the absorbance value after oil red O staining. EPO did not affect the proliferation activity of MSCs. EPO could down-regulate the expression of PPAR 纬 -C / EBP 伪 -FABP4 and adiponectin mRNA in adipogenic process. The phosphorylation of ERKN p38 MAPK and PPAR 纬 proteins during differentiation was increased. Conclusion the expression of PPAR 纬 may be down-regulated by increasing the phosphorylation of p38 MAPK and ERK proteins. C / EBP 伪 -FABP4 and adiponectin mRNA were expressed to inhibit adipogenic differentiation of MSCs.
【作者单位】：暨南大学血液病研究所;
【基金】：国家自然科学基金资助项目(No.81270568)
【分类号】：R329.28
【正文快照】： 在哺乳动物体内,促红细胞生成素(erythropoie-tin,EPO)是一种由肾脏及胎肝产生的糖蛋白。低氧条件下,EPO与其受体(EPO receptor,EPO-R)结合发挥作用,促进红系祖细胞增殖、分化为成熟红细胞,以增加循环中红细胞数量[1]。目前临床上主要用于治疗外科手术、慢性肾功能衰竭、化疗

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