HMGB1/SREBP-1参与IFN-γ介导的小鼠肾小球系膜细胞内的脂质沉积  

HMGB1/SREBP-1 mediated IFN-γ-induced lipid deposition in mouse mesangial cells

作　　者：张玉军[1,2] 陈砚凝[1,3] 郑书深[1] 刘青娟[1] 郝军[1] 韩嫣[4] 杨保卫 刘淑霞[1] 

机构地区：[1]河北医科大学病理教研室,石家庄050017 [2]石家庄人民医学高等专科学校,石家庄050091 [3]河北医科大学第四医院病理科,石家庄050012 [4]河北医科大学,石家庄050017 [5]解放军总参三部保定干休所卫生所,河北保定071000

出　　处：《中国应用生理学杂志》2013年第1期6-10,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金(81000301);河北省自然科学基金(C2010000463);河北省教育厅资助项目(Z2009151)

摘　　要：目的:探讨γ-干扰素(IFN-γ)诱导小鼠系膜细胞内脂质沉积的可能机制。方法:常规培养的小鼠系膜细胞(MMC)分为正常对照组、刺激组、刺激+空质粒组(sh-HMGB1)和刺激+质粒组(sh-SREBP-1);油红O染色观察细胞内脂质沉积;RT-PCR检测HMGB1、SREBP-1和脂肪酸合成酶(FAS)mRNA表达;Wesern blot检测蛋白表达。结果:油红O检测显示IFN-γ刺激组MMC细胞中出现明显脂滴;IFN-γ刺激能够上调HMGB、SREBP-1和FASmRNA及蛋白表达;沉默HMGB1能够降低IFN-γ诱导的SREBP-1和FAS上调,并减少细胞内脂质沉积;沉默SREBP-1能够减少HMGB诱导的MMC细胞内脂质沉积。结论:IFN-γ可能通过上调HMGB/SREBP-1/FAS的表达促进小鼠系膜细胞内脂滴沉积。Objective： To explore the possible mechanism of lipid deposition induced by interferon-γ（IFN-γ）.Methods： The mouse mesangial cells（MMC） were randomly divided into control group,stimulation group,stimulation＋control vector group（sh-HMGB1） and stimulation＋specific sh-vector group（sh-SREBP-1）. RTPCR was used to detect the expression of HMGB1,SREBP-1 and fatty acid synthetase（FAS） mRAN;the protein expression was determined by Western blot.Results： The Oil Red O staining revealed that the mouse mesangial cells showed significant lipid droplet in IFN-γ group.IFN-γ up-regulated the expression of HMGB1,SREBP-1,FAS mRNA and protein time-dependently;Transfection of MMC with HMGB1 siRNA resulted in the suppression of SREBP-1,FAS protein levels induced by IFN-γ,following with decrease of lipid deposition.Stimulation with HMGB1 markedly induced expression of SREBP-1,FAS expression and peaked at 8 h,decreased at 12 h compared with that at 8 h.Sh-SREBP-1 decreased the lipid deposition induced by HMGB1 in MMC.Conclusion： IFN-γ might induce lipid deposition in mouse mesangial cells partly by up-regulating the expression of HMGB1/SREBP-1/FAS.

关 键 词：IFN-Γ 小鼠系膜细胞 脂质沉积 高迁移率族蛋白1 固醇调节元件结合蛋白-1 

分 类 号：R363[医药卫生—病理学] R593[医药卫生—基础医学]