Department of Biochemistry Federal University of São Paulo (UNIFESP), Brazil.
Department of Biophysics Federal University of São Paulo (UNIFESP), Brazil.
Biochimie. 2019 Nov;166:173-183. doi: 10.1016/j.biochi.2019.04.011. Epub 2019 Apr 12.
Formation of new blood vessels from preexisting ones, a process known as angiogenesis, is one of the limiting steps for success in treatment of ischemic disorders. Therefore, efforts to understanding and characterize new agents capable to stimulate neovascularization are a worldwide need. Crataeva tapia bark lectin (CrataBL) has been shown to have chemoattractant properties for endothelial cells through the stimulation of migration and invasiveness of human umbilical vein endothelial cells (HUVEC) because it is a positively charged protein with high affinity to glycosaminoglycan. In addition, CrataBL increased the production of chondroitin and heparan sulfate in endothelial cells. These findings orchestrated specific adhesion on collagen I and phosphorylation of tyrosine kinase receptors, represented by vascular endothelial growth factor receptor-2 (VEGFR-2) and fibroblast growth factor receptor (FGFR), whose downstream pathways trigger the angiogenic cascade increasing cell viability, cytoskeleton rearrangement, cell motility, and tube formation. Moreover, CrataBL inhibited the activity of matrix metalloproteases type 2 (MMP-2), a protein related to tissue remodeling. Likewise, CrataBL improved wound healing and increased the number of follicular structures in lesioned areas produced in the dorsum-cervical region of C57BL/6 mice. These outcomes altogether indicate that CrataBL is a pro-angiogenic and healing agent.
从预先存在的血管中形成新的血管,这一过程称为血管生成,是治疗缺血性疾病成功的限制步骤之一。因此,人们努力理解和表征新的能够刺激新血管形成的药物,这是全世界的需求。白花丹科植物 Crataeva tapia 的树皮凝集素 (CrataBL) 已被证明具有趋化特性,可通过刺激人脐静脉内皮细胞 (HUVEC) 的迁移和侵袭来发挥作用,因为它是一种带正电荷的蛋白质,对糖胺聚糖具有高亲和力。此外,CrataBL 增加了内皮细胞中软骨素和肝素硫酸盐的产生。这些发现协调了特定的粘附在胶原蛋白 I 上,以及酪氨酸激酶受体的磷酸化,这些受体由血管内皮生长因子受体-2 (VEGFR-2) 和成纤维细胞生长因子受体 (FGFR) 代表,其下游途径触发血管生成级联反应,增加细胞活力、细胞骨架重排、细胞迁移和管状结构形成。此外,CrataBL 抑制了基质金属蛋白酶 2 (MMP-2) 的活性,MMP-2 是一种与组织重塑相关的蛋白质。同样,CrataBL 促进了伤口愈合,并增加了 C57BL/6 小鼠颈背部损伤区域的毛囊结构数量。所有这些结果都表明,CrataBL 是一种促血管生成和愈合剂。