当前位置: X-MOL 学术Life Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Nuclear accumulation of pyruvate kinase M2 promotes liver regeneration via activation of signal transducer and activator of transcription 3.
Life Sciences ( IF 6.1 ) Pub Date : 2020-03-19 , DOI: 10.1016/j.lfs.2020.117561
Kai Hu 1 , Juanjuan Xu 2 , Kerui Fan 2 , Dan Zhou 3 , Longjiang Li 2 , Li Tang 2 , Xianwen Peng 2 , Li Zhang 2 , Yaping Wang 2
Affiliation  

AIMS Pyruvate kinase M2 (PKM2), a unique isoform of the pyruvate kinases, not only acts as a crucial metabolic enzyme when it locates in the cytoplasm, but also plays important roles in tumor formation and growth when it accumulates in the nuclei. Our aim was to investigate the potential role of PKM2 in liver regeneration in mice insulted with carbon tetrachloride (CCl4). MATERIAL AND METHODS The liver regeneration model was established by intraperitoneal injection of CCl4 for 48 h in male BALB/c mice. The expression of PKM2, phospho-STAT3, STAT3, proliferating cell nuclear antigen (PCNA) and Cyclin D1 were evaluated by western blot. The distribution of PKM2 was verified by immunofluorescence staining. The degree of injured region was assessed by hematoxylin and eosin (HE) staining. The proliferation of liver cells was tested by Immunohistochemistry. KEY FINDINGS The nuclear accumulation of PKM2 increased in the liver treated with CCl4, but treatment with ML-265 significantly suppressed CCl4-induced nuclear accumulation of PKM2. In addition, treatment with ML-265 suppressed the level of cyclin D1 and proliferating cell nuclear antigen (PCNA), reduced the count of Ki67-positive hepatocytes, and expanded the damaged region in histological examination. Meanwhile, treatment with ML-265 suppressed the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 by stattic made the same effects as ML-265. SIGNIFICANCE These data uncovered the role of nuclear PKM2 in liver regeneration and the pro-proliferation effects of nuclear PKM2 may be through targeting its downstream transcription factor STAT3.

中文翻译:

丙酮酸激酶M2的核积累通过信号转导子和转录激活子的激活促进肝脏再生3。

AIMS丙酮酸激酶M2(PKM2)是丙酮酸激酶的独特同种型,不仅位于细胞质中时起着至关重要的代谢酶的作用,而且在细胞核中积累时在肿瘤形成和生长中也起着重要作用。我们的目的是研究PKM2在四氯化碳(CCl4)损伤的小鼠肝脏再生中的潜在作用。材料与方法雄性BALB / c小鼠腹腔注射CCl4 48 h建立肝再生模型。Western blot检测PKM2,磷酸化STAT3,STAT3,增殖细胞核抗原(PCNA)和细胞周期蛋白D1的表达。通过免疫荧光染色证实了PKM2的分布。通过苏木精和曙红(HE)染色评估受损区域的程度。通过免疫组织化学测试肝细胞的增殖。主要发现用CCl4处理的肝脏中PKM2的核积累增加,但是用ML-265处理可显着抑制CCl4诱导的PKM2核积累。此外,用ML-265处理可抑制细胞周期蛋白D1和增殖细胞核抗原(PCNA)的水平,减少Ki67阳性肝细胞的数量,并扩大组织学检查的受损区域。同时,用ML-265处理可抑制核信号转导子和转录激活子3(STAT3)的磷酸化。STAT3对STAT3的抑制作用与ML-265相同。
更新日期:2020-03-20
down
wechat
bug