College of Medicine, CHA University, CHA General Hospital, Gyeonggi-Do 463-840, Republic of Korea.
J Cell Biochem. 2013 Feb;114(2):303-13. doi: 10.1002/jcb.24370.
In our previous study, we screened and isolated genes that were up-regulated after partial pancreatectomy using transcriptomic analysis and glutamate-ammonia ligase (GLUL) was selected for further study based on its effect on differentiation and proliferation. In the immunohistochemical analysis, GLUL was highly up-regulated in the acinar cells and the ductal cells in the pancreas damaged through partial pancreatectomy. Overexpression of GLUL enhanced the proliferation of PANC-1 cells and INS-1 cells. GLUL overexpression shifted the major population of PANC-1 cells from the G0/G1 phase to G2/M phase. In the double thymidine blocking analysis, similar cycle duration was observed between mock cells and GLUL-overexpressing cells while GLUL-overexpressing cells were partially resistant to thymidine blocking. In the FACS analysis of cells stained with Pyronin Y and Hoechst 33342, GLUL-overexpressing cells showed lower population of cells in the G0-quiescent phase than mock cells (5-12%). In addition, GLUL-overexpressing cells had high activation levels of AKT, ERK1/2, JNK, PCNA, c-FOS, and P70S6K in PANC-1 cells. Taken together, these results suggest that GLUL contributes to pancreatic regeneration.
在我们之前的研究中,我们使用转录组分析筛选并分离了部分胰腺切除后上调的基因,根据其对分化和增殖的影响,选择谷氨酸-氨甲酰基转移酶 (GLUL) 进行进一步研究。在免疫组织化学分析中,GLUL 在通过部分胰腺切除损伤的胰腺腺泡细胞和导管细胞中高度上调。GLUL 的过表达增强了 PANC-1 细胞和 INS-1 细胞的增殖。GLUL 的过表达将 PANC-1 细胞的主要群体从 G0/G1 期转移到 G2/M 期。在双胸苷阻断分析中,在模拟细胞和 GLUL 过表达细胞之间观察到相似的周期持续时间,而 GLUL 过表达细胞对胸苷阻断有部分抗性。在用 Pyronin Y 和 Hoechst 33342 染色的细胞的 FACS 分析中,GLUL 过表达细胞的 G0 静止期细胞群比模拟细胞少(5-12%)。此外,GLUL 过表达细胞在 PANC-1 细胞中 AKT、ERK1/2、JNK、PCNA、c-FOS 和 P70S6K 的激活水平较高。综上所述,这些结果表明 GLUL 有助于胰腺再生。