Study on the role of Cathepsin B and JNK signaling pathway in the development of cerebral aneurysm

• Published in: Asian Pacific journal of tropical medicine Vol. 9; no. 5; pp. 485 - 488
• Main Authors: Guo, Dong, Wang, Ye-Wei, Ma, Ji, Yan, Lei, Li, Teng-Fei, Han, Xin-Wei, Shui, Shao-Feng
• Format: Journal Article
• Language: English
• Published: India Elsevier B.V 01.05.2016
• Subjects: analysis; aneurysm;Cathepsin; B;JNK; Cathepsin B; Cerebral; Cerebral aneurysm; Correlation analysis; JNK signaling pathway; pathway;Correlation; Signaling; Cathepsin B; Cerebral aneurysm; JNK signaling pathway; Correlation analysis
• ISSN: 1995-7645; 2352-4146; 2352-4146
• DOI: 10.1016/j.apjtm.2016.03.020

Objective: To investigate the correlation between JNK signal and the apoptosis of VSMC as well as the expression of Cathepsin B and to explore the role of JNK signal in the development of cerebral aneurysm. Methods: Rat models of cerebral aneurysm were established and histopathologic changes of cerebral aneurysm and the apoptosis of VSMC were analyzed. Rat models were respectively subject to subcutaneous injection of Cathepsin B si RNA and JNK inhibitor SP600125. Western blot technique was used to detect the expression of proteins like Cathepsin B, Caspase-3, and p-JNK. Spearman’s rho was used to examine the correlation between p-JNK and Cathepsin B, as well as the expression of relevant proteins. Results:The success rate of modeling rats with cerebral aneurysm was 88.75%. After the respective injection of Cathepsin B si RNA, SP600125 and their combination, the cell densities of VSMC of rats with cerebral aneurysm all increased significantly(P<0.05 or P<0.01), but the apoptosis rate of VSMC decreased significantly(P<0.01). Compared with normal rats, the expression of Cathepsin B, Caspase-3 and p-JNK in cerebral aneurysm models increased significantly. Effectively intervening Cathepsin B genes with Cathepsin B si RNA could significantly inhibit the expression of Cathepsin B and Caspase-3, but hardly influence the expression of p-JNK. JNK inhibitor SP600125 had no influence on the expression of Cathepsin B and Caspase-3, but effectively inhibited the expression of p-JNK. In cerebral aneurysm tissues, positive correlation was observed between the expression of p-JNK and Cathepsin B, the correlation coefficient was r=0.640. Conclusion: After the attack of cerebral aneurysm, proteins like Cathepsin B, Caspase-3 and p-JNK are all involved in the apoptosis of VSMCs. This process may be realized by Cathepsin B which activates the apoptosis mechanism of Caspase-3 and mediate the apoptosis of VSMC through the JNK signaling pathway. Therefore, silencing Cathepsin B gene or inhibiting the conduction through JNK signaling pathway can mitigate the apoptosis of vascular smooth muscle cells in cerebral aneurysm.