STAT蛋白在抑瘤素M诱导的肾小管上皮细胞损伤中的作用  

Role of STAT in renal tubular epithelial cell injury induced by oncostatin M

作　　者：李建英[1] 杜云霞[2] 张玮[2] 张瑞华[3] 封晓娟[2] 刘思媛[2] 刘青娟[2] 

机构地区：[1]河北省石家庄市第一医院皮肤科,石家庄050011 [2]河北医科大学病理学教研室,石家庄050017 [3]河北医科大学第一医院病理科,石家庄050030

出　　处：《临床与实验病理学杂志》2016年第2期184-187,共4页Chinese Journal of Clinical and Experimental Pathology

基　　金：教育部高等学校博士学科点专项科研基金(新教师类20131323120001);2012年河北省科学技术研究与发展计划项目(12277724)

摘　　要：目的探讨STAT蛋白在抑瘤素M(oncostatin M,OSM)诱导的肾小管上皮细胞表型转化及分泌功能中的作用。方法体外培养人肾近曲小管上皮细胞,分为对照组(C组)、OSM(20 ng/ml)组(OSM组)、OSM+雷帕霉素(100 ng/ml)组(OSM+R组)和OSM+氟达拉滨(100 ng/ml)组(OSM+F组)。培养72 h后收集细胞及上清液,透射电镜观察细胞超微结构改变;免疫细胞化学和Western blot法检测CK18、α-SMA蛋白表达;采用Western blot法检测信号转导及转录激活因子(STAT1、STAT3、pSTAT1、p-STAT3)的表达;酶联免疫吸附实验测定细胞上清液中Ⅰ型胶原(collagenⅠ,ColⅠ)和纤维连接蛋白(fibronectin,FN)的分泌。结果与对照组相比,细胞经OSM刺激后CK18的表达下调,而α-SMA的表达上调并分泌过多的细胞外基质蛋白ColⅠ和FN;此外,OSM还可磷酸化激活STAT1和STAT3。OSM的上述作用可被雷帕霉素和氟达拉滨所阻断。结论 OSM具有促纤维化特性,而STAT1和STAT3信号活化在OSM介导的纤维化进程中发挥同等重要的作用。Purpose To investigate the role of STAT in renal tubular epithelial injury induced by oncostatin M （OSM）. Methods Cells were divided into four groups： control group, OSM （20 ng/ml） group, OSM ＋ rapamycin （100 ng/ml） （OSM ＋ R） and OSM ＋ fludarabine （100 ng/ml） （OSM ＋ F） group. Cells and supernatant were collected after 72 h induced by OSM. The cells ultrastructure was observed by transmission electron microscopy. The protein expression of CK18 and α-SMA was observed by immunocytochemistry and Western blot. STAT1, STAT3, p-STAT1 and p-STAT3 were analyzed by Western blot. The protein secretion of Col Ⅰ and FN in the supernatants was detected by enzyme-linked immunoadsorbent assay （ELISA）. Results Compared with control group, the expres- sion level of CK18 protein decreased while the expression level of α-SMA protein increased after OSM stimulation. There was a higher concentration of Col I and FN in the supernatants with OSM stimulation. In addition, OSM induced the activation of STAT1 and STAT3. Moreover, both fludarabine and rapamycin had inhibitory effect on the role of OSM. Conclusion OSM is a profibrotic factor. The activation of STAT1 and STAT3 plays an equally important role in fibrosis induced by OSM.

关 键 词：肾小管上皮细胞 抑瘤素M 信号转导及转录激活因子 上皮-间质转化 

分 类 号：R692.6[医药卫生—泌尿科学]