粘着斑相关蛋白Kindlin-1在血管内皮细胞的表达及功能研究  

Expression and function of the focal adhesion protein Kindlin-1 in endothelial cells

作　　者：吴晓昊 陶楚 姚青 伏学坤 梁超 曹惠玲 肖国芝 Wu Xiaohao;Tao Chu;Yao Qing;Fu Xuekun;Liang Chao;Cao Huiling;Xiao Guozhi(School of Medicine,Southern University of Science and Technology,Shenzhen Guangdong,518055;School of Life Science,Southern University of Science and Technology,Shenzhen Guangdong,518055,China)

机构地区：[1]南方科技大学医学院,广东深圳518055 [2]南方科技大学生命科学学院,广东深圳518055

出　　处：《生物骨科材料与临床研究》2021年第3期18-23,共6页Orthopaedic Biomechanics Materials and Clinical Study

基　　金：国家重点研发计划(2019YFA0906004);国家自然科学基金(81991513)。

摘　　要：目的探索Kindin-1蛋白在健康骨关节组织及关节炎模型骨关节组织中的表达模式及相关功能。方法分离健康小鼠、经内侧半月板失稳定术(DMM)诱导关节炎小鼠以及经胶原诱导关节炎(CIA)小鼠的骨关节组织,通过抗体免疫荧光标记分析Kindlin-1蛋白在骨关节组织内的表达情况。筛选针对Kindlin-1的siRNA序列并进行体外功能验证。结果免疫荧光分析发现Kindlin-1主要表达于健康骨组织的骨髓腔中,进一步发现Kindlin-1信号与骨内H型血管(由CD31和Endomucin共同标记)存在共定位。在DMM和CIA模型中,Kindlin-1表达量均显著升高并可特异性地标记异常的新生血管。在人类脐静脉血管内皮细胞(HUVECs)中也可检测到Kindlin-1的高水平表达。通过siRNA敲除Kindlin-1可显著地增强HUVECs的体外迁移能力。结论粘着斑相关蛋白Kindlin-1表达于血管内皮细胞,并可作为骨关节组织内血管组织及异常血管新生的生物标志及潜在靶点。Objective To investigate the expression pattern and associated function of Kindlin-1 in healthy bone tissue and arthritic bone tissue.Methods Bone tissue was separated from healthy mice,mice with destabilization of themedialmeniscus(DMM)surgery-induced arthritis,and mice with collagen-induced arthritis(CIA).Immunofluorescent staining was used to analyze the expression of Kindlin-1 in bone tissue.siRNA sequence targeting Kindlin-1 was screened and applied for in vitro experiments.Results Immunofluorescent staining revealed that Kindlin-1 was mainly expressed in the bone marrow cavities of healthy bone tissue cavities.Kindlin-1 was further found to co-localized with type H vessels,which expressed both CD31 and Endomucin.In DMM-induced arthritis and CIA,Kindlin-1 expression was dramatically increased and could specifically label abnormal nascent blood vessels.Furthermore,Kindlin-1 was also highly expressed in human umbilical vein endothelial cells(HUVECs).siRNA knockdown of Kindlin-1 expression markedly accelerated the migration ability of HUEVCs in vitro.Conclusion Kindlin-1 is expressed in endothelial cells and may be the biomarker and potential target of angiogenesis in bone tissue under physiological and pathological conditions.

关 键 词：Kindlin-1 内皮细胞 骨生物学 血管新生 H型血管 

分 类 号：R363[医药卫生—病理学]