Regulatory mechanism of MiR-21 in formation and rupture of intracranial aneurysm through JNK signaling pathway-mediated inflammatory response.

Objective: To investigate the regulatory mechanism of micro ribonucleic acid (miR)-21 in the formation and rupture of intracranial aneurysm through the c-Jun N-terminal kinase (JNK) signaling pathway-mediated inflammatory response.

Methods: In the present study, the mice with miR-21 expression deficiency and over-expression in our laboratory were enrolled as the experimental group, while wild-type healthy mice were used as the control group. The mouse model of intracranial aneurysm was established by bilateral carotid artery ligation. The differences in the levels of key genes in the JNK signaling pathway (JNK1 and JNK2) were detected by fluorescence quantitative polymerase chain reaction (qPCR) and western blotting. At the same time, the changes in transcription and translation levels of inflammatory factors, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in both groups were measured. After the mice were executed by an overdose of anesthesia, the morphology of the aneurysm in different objects was observed by Verhoeff-Van Gieson (EVG) staining and the expressions of TNF-α, JNK1, and JNK2 were determined by immunohistochemistry.

Results: Compared with healthy mice, levels of JNK1 and JNK2 in mice with miR-21 deficiency were significantly decreased ( < 0.05) with a significant reduction of inflammatory factors IL-6 and TNF-α ( < 0.05). Compared with healthy mice, levels of JNK1 and JNK2 in mice with miR-21 over-expression were significantly increased ( < 0.05) with significant growing levels of inflammatory factors IL-6 and TNF-α ( < 0.05). The results of EVG staining revealed that the intracranial aneurysm was smaller in mice with miR-21 deficiency [(0.3 ± 0.12) cm] and larger in mice with miR-21 over-expression [(0.8 ± 0.25) cm] and there was a significant difference ( < 0.05). Moreover, the results of immunohistochemistry showed that the expression of TNF-α in intracranial aneurysm was obviously lower in mice with miR-21 deficiency than that in mice with miR-21 over-expression.

Conclusion: MiR-21 can promote the production of inflammation-related factors through the JNK signaling pathway, leading to the formation and rupture of an intracranial aneurysm.