Cras Audrey, Larghero Jérôme, Rossi Elisa, Blandinières Adeline, Gaussem Pascale, Smadja David M
Université de Paris Cité, INSERM, Innovative Therapies in Hemostasis, F-75006, Paris, France.
Cell therapy unit, AP-HP, Saint Louis Hospital, F-75010, Paris, France.
Stem Cell Rev Rep. 2023 Oct;19(7):2541-2550. doi: 10.1007/s12015-023-10587-1. Epub 2023 Jul 15.
Nestin, an intermediate filament protein expressed by progenitor cells, is associated with tissue regeneration. Although nestin expression has been reported in poorly differentiated and newly formed blood vessels, its role in endothelial cells remains unclear. In this study, we investigated the involvement of nestin in the angiogenic properties of endothelial colony-forming cells (ECFCs) derived from human umbilical cord blood. Our results demonstrate that ECFCs express high levels of nestin, and that its inhibition by small interfering RNAs decreased ECFC proliferation, migration in response to SDF-1 and VEGF-A, tubulogenesis, and adhesion on collagen. These effects are associated with modulation of focal adhesion kinase phosphorylation. Furthermore, nestin silencing resulted in reduced revascularization in a mouse hindlimb ischemia model. In conclusion, these findings provide evidence that nestin more than being a structural protein, is an active player in ECFC angiogenic properties.
巢蛋白是一种由祖细胞表达的中间丝蛋白，与组织再生相关。尽管已有报道称巢蛋白在低分化和新形成的血管中表达，但其在内皮细胞中的作用仍不清楚。在本研究中，我们调查了巢蛋白在源自人脐带血的内皮集落形成细胞（ECFCs）血管生成特性中的作用。我们的结果表明，ECFCs表达高水平的巢蛋白，并且小干扰RNA对其的抑制作用降低了ECFC的增殖、对SDF-1和VEGF-A的迁移反应、管腔形成以及在胶原蛋白上的黏附。这些效应与粘着斑激酶磷酸化的调节有关。此外，在小鼠后肢缺血模型中，巢蛋白沉默导致血管再生减少。总之，这些发现提供了证据，表明巢蛋白不仅仅是一种结构蛋白，还是ECFC血管生成特性中的一个活跃参与者。
