Tominaga Shin-Ichi, Ohta Satoshi, Tago Kenji
Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan.
Biochem Biophys Rep. 2015 Nov 21;5:8-15. doi: 10.1016/j.bbrep.2015.11.020. eCollection 2016 Mar.
The ST2 gene is induced in murine fibroblast cells at the start of cell proliferation. Although IL-33 has been identified as a ligand for one of the two major gene products of ST2 - namely, the transmembrane receptor form ST2L - prompting immunological research on inflammation, the roles of the ST2 gene products in cell proliferation remain to be elucidated. Using a cell proliferation assay system with NIH-3T3 cells, a normal murine fibroblast cell line, we found that treatment with recombinant ST2 caused an acceleration of cell proliferation, suggesting that ST2 acts in an autocrine/paracrine fashion. Strikingly, shRNA-induced knockdown of both ST2 gene products, ST2 and ST2L, reduced cell proliferation. This effect was effectively canceled by the expression of shRNA-resistant ST2, but not shRNA-resistant ST2L. The novel enhancement of cell proliferation by ST2 appears to involve positive feedback. Since the ST2 level is increased in various diseases involving inflammation, future investigations into the role of ST2 gene products in relation to various diseases, including malignancies, may be warranted.
ST2基因在小鼠成纤维细胞开始增殖时被诱导。尽管白细胞介素-33已被确定为ST2的两种主要基因产物之一（即跨膜受体形式的ST2L）的配体，这推动了关于炎症的免疫学研究，但ST2基因产物在细胞增殖中的作用仍有待阐明。使用具有正常小鼠成纤维细胞系NIH-3T3细胞的细胞增殖检测系统，我们发现用重组ST2处理会导致细胞增殖加速，这表明ST2以自分泌/旁分泌方式起作用。引人注目的是，shRNA诱导的ST2基因产物ST2和ST2L的敲低会降低细胞增殖。shRNA抗性ST2的表达有效地消除了这种作用，但shRNA抗性ST2L则没有。ST2对细胞增殖的这种新的增强作用似乎涉及正反馈。由于ST2水平在各种炎症相关疾病中升高，未来对ST2基因产物在包括恶性肿瘤在内的各种疾病中的作用进行研究可能是必要的。
