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评估 MK1 细菌菌株产生的新型胞外多糖的血管生成能力。

Evaluation of the angiogenic potency of a novel exopolysaccharide produced by the MK1 bacterial strain.

机构信息

Bonecell Biotech Inc., 77, Dunsan-dong, Seo-gu, Daejeon, 302-830, Korea.

Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, 570-749, Korea.

出版信息

Arch Pharm Res. 2016 Sep;39(9):1223-31. doi: 10.1007/s12272-016-0776-y. Epub 2016 Jun 29.

DOI:10.1007/s12272-016-0776-y
PMID:27357535
Abstract

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.

摘要

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。

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Arch Pharm Res. 2016 Sep;39(9):1223-31. doi: 10.1007/s12272-016-0776-y. Epub 2016 Jun 29.
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