Abstract
Intracranial aneurysm (IA) rupture is a major cause of stroke death. Alteration of vascular smooth muscle cell (VSMC) function and phenotypic modulation plays a role in aneurysm progression. In the present study, we investigated the role of Annexin A3 (ANXA3) silencing in IA with the interaction of the c-Jun N-terminal kinase (JNK) signaling pathway. In IA and VSMCs of IA, the relationship between ANXA3 and the JNK signaling pathway was verified. To investigate the specific mechanism of ANXA3 silencing in IA, we transfected VSMCs with the overexpressed or small interfering RNA (siRNA) of ANXA3, or treated them with an inhibitor of the JNK signaling (SP600125). Cell counting kit-8 (CCK-8) assay was conducted to detect cell viability, and flow cytometry was conducted to assess cell cycle and apoptosis so as to evaluate the gain- and loss-of-function of ANXA3 and investigate the involvement of the JNK signaling pathway. The aneurysm wall of IA cells demonstrated an elevated level of ANXA3 expression and an activated JNK signaling pathway. VSMCs treated with siRNA-ANXA3 or SP600125 showed decreased expression of JNK, caspase-3, osteopontin (OPN), Bax, and matrix metalloproteinase-9 (MMP-9), as well as phosphate (p)-JNK, but increased the expression of α smooth muscle actin (α-SMA), β-tubulin, and Bcl-2. ANXA3 silencing or inactivation of the JNK signaling pathway also enhanced proliferation and repressed apoptosis of VSMCs. Collectively, this study shows that the silencing of ANXA3 can rescue VSMC function in IAs by inhibiting the phosphorylation and activation of the JNK signaling pathway. These findings may provide a potential therapy for the molecular treatment of IAs.