CAJ | 학술논문

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.
이P19CL6소서기태류세포심기분화위모형,연구료p38신호통로재간세포심기분화조기계단적작용.재유도제이갑기아풍작용하,P19CL6세포분화위자발도동적심기세포,표체심기표지성기인.재유도분화과정중,p38신호통로활화.채용특이성억제제SB203580재조기분화계단봉폐p38신호통로,결과발현：고제량SB203580유도세포조망；저제량SB203580억제심기조세포표지기인GATA4화Nkx2.5적표체,병현저하조생심성신호분자BMP2화BMP4적표체.이과표체p38α질립칙능촉진P19CL6세포표체GATA4화Nkx2.5.표명p38신호통로정성조공P19CL6세포적조기심기분화,병유지세포적증식화존활능력.
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.