目的:探讨激活蛋白1(AP1)家族成员在子宫肌瘤细胞外基质沉积中的作用。
方法:实验室研究。
方法:大学研究实验室。
方法:平滑肌瘤和子宫肌层细胞系暴露于单独的AP1抑制剂,AP1抑制剂加转化生长因子(TGF)β3,或单独TGFβ3。
方法:进行Western免疫印迹分析以评估AP1家族成员蛋白表达的变化。
结果:在患者匹配的子宫肌层和平滑肌瘤细胞系中,与子宫肌层相比,在平滑肌瘤中发现显着升高的唯一AP1成员是FOSB(3.47±0.12倍),而其他则显着降低:FRA1(0.67±0.02倍),FRA2(0.45±0.01倍),cFOS(0.37±0.01倍),PhoscFOS(0.19±0.02倍),PhoscJUN(0.75±0.02倍),JUNB(0.81±0.04倍),和JUND(0.65±0.03倍)。cJUN(0.93±0.03倍)浓度降低,但水平不显着。用TGFβ3刺激后,纤连蛋白(2.16±0.14倍)和versican(4.71±0.15倍)的蛋白质浓度在24小时时增加。胶原蛋白1A表现出时间依赖性的显着增加,从6小时开始(1.32±0.01倍),并在24小时时增加到(6.49±0.02倍)。用AP1抑制剂(SR11302)治疗后,胶原1A浓度在4小时(0.59±0.03倍)和6小时(0.42±0.05倍)时显著降低。激活剂蛋白1抑制直到处理6小时才显著降低versican浓度(0.84±0.04倍)。SR11302还在处理8小时时显著降低纤连蛋白浓度(0.68±0.05倍)。
结论:激活蛋白1信号在纤维化疾病中有很好的描述,and,在这里,我们证明通过AP1家族成员的信号传导促进平滑肌瘤的细胞外基质沉积。
OBJECTIVE: To characterize the role Activator Protein 1 (AP 1) family members play in mediating extracellular matrix deposition in uterine leiomyoma.
METHODS: Laboratory study.
METHODS: University research laboratory.
METHODS: Exposure of leiomyoma and myometrial cell lines to either an AP 1 inhibitor alone, AP 1 inhibitor plus transforming growth factor (TGF)ß3, or TGFß3 alone.
METHODS: Western immunoblot analysis was performed to assess for changes in AP 1 family member protein expression.
RESULTS: In patient-matched myometrial and leiomyoma cell lines, the only AP 1 member found to be elevated significantly in leiomyoma compared with myometrium was FOSB (3.47 ± 0.12-fold), whereas others were decreased significantly: FRA1 (0.67 ± 0.02-fold), FRA2 (0.45 ± 0.01-fold), c FOS (0.37 ± 0.01-fold), Phos c FOS (0.19 ± 0.02-fold), Phos c JUN (0.75 ± 0.02-fold), JUNB (0.81 ± 0.04-fold), and JUND (0.65 ± 0.03-fold). c JUN (0.93 ± 0.03-fold) concentration was reduced but at nonsignificant levels. Following stimulation with TGF ß 3, fibronectin (2.16 ± 0.14-fold) and versican (4.71 ± 0.15-fold) protein concentrations were increased at 24 hours. Collagen 1A demonstrated a time-dependent significant increased concentration beginning at 6 hours (1.32 ± 0.01-fold) and increased to (6.49 ± 0.02-fold) at 24 hours. Following treatment with AP 1 inhibitor (SR11302), there were significant reductions in Collagen 1A concentration at 4 hours (0.59 ± 0.03-fold) and 6 hours (0.42 ± 0.05-fold). Activator Protein 1 inhibition did not reduce significantly versican concentration until 6 hours of treatment (0.84 ± 0.04-fold). SR11302 also decreased significantly fibronectin concentration (0.68 ± 0.05-fold) at 8 hours of treatment.
CONCLUSIONS: Activator Protein 1 signaling is well described in fibrotic diseases, and, herein, we demonstrated that signaling via AP 1 family members promotes extracellular matrix deposition in leiomyoma.