ELK1-CDKL5-Rac1 signaling pathway regulates the migration of endothelial cells to promote angiogenesis induced by nanoniobium particles  

作　　者：Xiao-He Zhou Min-Hua Mo Zi-Wei Chen Wen-Jing Liu Yan-Li Zhang Janak LPathak Li-Jing Wang Chang Liu Long-Quan Shao Liang-Jiao Chen 

机构地区：[1]Department of Orthodontics,School and Hospital of Stomatology,Guangdong Engineering Research Center of Oral Restoration and Reconstruction&Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine,Guangzhou Medical University,Guangzhou,510160,China [2]Stomatological Hospital,School of Stomatology,Southern Medical University,Guangzhou,510220,China

出　　处：《Rare Metals》2025年第1期444-460,共17页稀有金属(英文版)

基　　金：supported by Guangzhou Science and Technology Plan Project(No.2023A03J0328);the National Natural Science Foundation of China(No.81600904)。

摘　　要：Promotion of angiogenesis is crucial for bone tissue repair,and the poor activity of angiogenic cells and growth factors is the main problem in angiogenesis.New proangiogenic nanomaterials are urgently needed to be a promising strategy for this issue.Nb promotes bone formation and fracture healing,possibly by increasing vascular endothelial growth factor(VEGF)production.Nanoniobium particles(nNb)may promote angiogenesis.However,the effect of nNb on angiogenesis is unclear,limiting its application.This study confirmed that nNb significantly promoted angiogenesis.nNb increased and Ras-related C3 botulinum toxin substrate(Rac)family small guanosine triphosphatase(GTPase)1(Rac1)expression,inducing F-actin aggregation at the front edge of cells and the formation of pseudopodia to mediate cell migration,further promoting angiogenesis.We discovered that cyclin-dependent kinase-like 5(CDKL5)is a new signaling molecule that activates Rac1.V-ets erythroblastosis virus E26 oncogene homolog(ETS)domain-containing protein(ELK1),regulating CDKL5 and Rac1,plays an upstream regulatory role.When ELK1 was inhibited,CDKL5 and Rac1 levels were decreased.ELK1,CDKL5 or Rac1 are effective regulatory targets of angiogenesis.Inhibiting expression of ELK1,CDKL5 or Rac1 decreased angiogenesis.Thus,nNb has good angiogenic effects.The ELK1-CDKL5-Rac1 signaling pathway regulates the migration of endothelial cells to promote angiogenesis.nNb can be used in bone tissue engineering as a new nanomaterial,and it will promote the development of a new strategy for tissue engineering.

关 键 词：Nanoniobium particles ANGIOGENESIS Endothelial cells MIGRATION ELK1-CDKL5-Rac1 signaling pathway 

分 类 号：R73[医药卫生—肿瘤]