病毒性心肌炎
心肌炎
炎症
整合素
小发夹RNA
过继性细胞移植
肿瘤坏死因子α
细胞生物学
免疫学
整合素αM
渗透(HVAC)
癌症研究
细胞
生物
医学
T细胞
免疫系统
细胞培养
基因敲除
内科学
生物化学
遗传学
物理
热力学
作者
Xuejie Wu,Yawen Meng,Chao Wang,Yue Yan,Chunsheng Dong,Sidong Xiong
标识
DOI:10.1016/j.yjmcc.2017.11.001
摘要
Semaphorin7A (Sema7A) has been reported to play various roles in nerve axon growth, tumor suppression, and tissue remodeling, as well as regulation of intestinal inflammation diseases. Viral myocarditis (VMC) characterized by viral-myocardial-cell necrosis and inflammatory cell infiltration is a common clinical disease of the cardiovascular system. However, the role of Sema7A in coxsackievirus B3 (CVB3)-induced VMC has not been reported. In this study, we generated an acute VMC mouse model by CVB3 infection, and manipulated Sema7A expression by in vivo polyethyleneimine-mediated Sema7A down-regulation. Our results indicated that Sema7A was up-regulated in cardiomyocytes during VMC, and that Sema7A down-regulation following short hairpin RNA interference or mAb neutralization effectively protected mice from VMC. Additionally, reduced inflammatory responses were observed along with Sema7A down-regulation. Furthermore, adoptive transfer of α1β1-integrin macrophages exacerbated CVB3-induced myocarditis, suggesting the significance of α1β1-integrin macrophages in response to VMC. We observed that co-culture of neonatal myocardiocytes with macrophages increased the percentage of α1β1-integrin macrophages, while Sema7A neutralization reduced α1β1-integrin macrophages in heart tissue of VMC mice. These results demonstrated that Sema7A, as an inflammation regulator in CVB3-induced VMC, might interact with α1β1-integrin in macrophages to enhance the inflammatory response and aggravate disease severity. Our findings provided insight into the potential role of Sema7A as a therapeutic treatment for VMC.
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