p38信号通路参与P19CL6细胞早期心肌分化  

The effect of p38 cascade in the early differentiation of P19CL6 cells towards cardiomyocytes

作　　者：黄巧丽 李涛[1] 姜科声[1] 刘羿男[2] 李贤慧[3] 刘元伟[4] 

机构地区：[1]浙江师范大学化学与生命科学学院,浙江金华321004 [2]北京大学医学部细胞生物学系,北京100191 [3]武警后勤学院生物化学与分子生物学教研室,天津300162 [4]浙江医院心内科,浙江杭州310013

出　　处：《浙江师范大学学报（自然科学版）》2015年第1期95-102,共8页Journal of Zhejiang Normal University:Natural Sciences

基　　金：国家自然科学基金资助项目(31101057;31470082);浙江省自然科学基金资助项目(LY14C120001)

摘　　要：以P19CL6小鼠畸胎瘤细胞心肌分化为模型,研究了p38信号通路在干细胞心肌分化早期阶段的作用.在诱导剂二甲基亚砜作用下,P19CL6细胞分化为自发跳动的心肌细胞,表达心肌标志性基因.在诱导分化过程中,p38信号通路活化.采用特异性抑制剂SB203580在早期分化阶段封闭p38信号通路,结果发现:高剂量SB203580诱导细胞凋亡;低剂量SB203580抑制心肌祖细胞标志基因GATA4和Nkx2.5的表达,并显著下调生心性信号分子BMP2和BMP4的表达.而过表达p38α质粒则能促进P19CL6细胞表达GATA4和Nkx2.5.表明p38信号通路正性调控P19CL6细胞的早期心肌分化,并维持细胞的增殖和存活能力.It was estimated the effect of p38 cascade in the early stage of cardiac differentiation using P19 CL6 mouse pluripotent carcinoma stem cells. In the presence of DMSO, P19CL6 cells were successfully induced to differentiate into spontaneously contracting cardiomyocytes characterized by the expression of cardiac-specific genes. It was observed the activation of p38 cascade during the differentiation process. Treatment with a high concentration of SB203580, a specific inhibitor of p38 kinase, significantly induced apoptosis of P19CL6 cells. Meanwhile, SB203580 at a low concentration greatly hampered the expression of cardiac marker genes GATA4 and Nkx2.5 , and decreased the expression of cardiac differentiation-promoting factors such as BMP2 and BMP4. Additionally, overexpression of p38 α plasmids facilitated the expression of GATA4 and Nkx2. 5. Taken these together, these results indicated that p38 cascade exerted a positive effect on the early differentia-tion of P19CL6 cells, and played an important role in maintaining cell growth and survival.

关 键 词：P19CL6细胞 心肌分化 P38激酶 信号通路 

分 类 号：Q254[生物学—细胞生物学]