Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon, 302-830, Korea.
Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, 570-749, Korea.
Arch Pharm Res. 2016 Sep;39(9):1223-31. doi: 10.1007/s12272-016-0776-y. Epub 2016 Jun 29.
Angiogenesis is an essential physiological step in wound healing and other regenerative processes. Here, we evaluated the angiogenic properties of an exopolysaccharide (EPS) secreted by MK1 (MK1-EPS), a novel bacterial strain isolated from Neungee mushrooms. MK1-EPS significantly increased human umbilical vein endothelial cell (HUVEC) proliferation, migration, and vascular tube formation. MK1-EPS enhanced the phosphorylation of extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, which are mitogen-activated protein kinases. In addition, the expression of p21 and intercellular adhesion molecule 1 (ICAM1), and phosphorylation of signal transducer and activator of transcription 3 (STAT3), but not of protein kinase B (AKT), were increased. Specific inhibitors of p38 (SB203580), ERK (PD98059), and JNK (SP600125) inhibited MK1-EPS-induced HUVEC proliferation, tube formation, and cell migration, and partially attenuated MKI-EPS-induced expression of p21 and ICAM1, and STAT3 phosphorylation. After surgical implantation into rabbit calvarial bone defects, new blood vessel formation was significantly higher with MK1-EPS composite bone granules than with granules alone, and new bone formation increased significantly. Therefore, MK1-EPS induces angiogenesis and may have potential for use as a bone regeneration agent in bone tissue engineering applications.
血管生成是创伤愈合和其他再生过程中的一个基本生理步骤。在这里,我们评估了一种从 Neungee 蘑菇中分离出的新型细菌菌株 MK1 分泌的胞外多糖 (EPS) 的血管生成特性。MK1-EPS 显著促进人脐静脉内皮细胞 (HUVEC) 的增殖、迁移和血管管腔形成。MK1-EPS 增强了细胞外信号相关激酶 (ERK)、c-Jun N 末端激酶 (JNK) 和 p38 的磷酸化,这些都是丝裂原活化蛋白激酶。此外,p21 和细胞间黏附分子 1 (ICAM1) 的表达以及信号转导和转录激活因子 3 (STAT3) 的磷酸化增加,但蛋白激酶 B (AKT) 的磷酸化没有增加。p38 (SB203580)、ERK (PD98059) 和 JNK (SP600125) 的特异性抑制剂抑制了 MK1-EPS 诱导的 HUVEC 增殖、管腔形成和细胞迁移,并部分减弱了 MK1-EPS 诱导的 p21 和 ICAM1 的表达以及 STAT3 的磷酸化。在兔颅骨骨缺损的手术植入后,MK1-EPS 复合骨颗粒的新生血管形成明显高于单纯颗粒,新骨形成明显增加。因此,MK1-EPS 诱导血管生成,可能具有作为骨组织工程应用中骨再生剂的潜力。