Acetylshikonin attenuates angiotensin II-induced proliferation and motility of human brain smooth muscle cells by inhibiting Wnt/β-catenin signaling

• Published in: Human cell : official journal of Human Cell Research Society Vol. 31; no. 3; pp. 242 - 250
• Main Authors: Li, Zequn, Yan, Zhiyuan, Xu, Chunbo, Dong, Yiqun, Xiong, Ye, Dai, Yongyue
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.07.2018; Springer Nature B.V
• Subjects: Angiotensin; Angiotensin II; Biomedical and Life Sciences; Brain; c-Myc protein; Cell adhesion & migration; Cell Biology; Cell cycle; Cell migration; Cell proliferation; Cerebrovascular system; Cyclin D1; Gynecology; Hyperplasia; Life Sciences; Myc protein; Nuclear transport; Oncology; Phosphorylation; Reproductive Medicine; Research Article; S phase; Smooth muscle; Stem Cells; Surgery; Survivin; Western blotting; Wnt protein; Wound healing; β-catenin; Acetylshikonin; Proliferation; Wnt/β-catenin pathway; Angiotensin II; Cerebrovascular smooth muscle cells
• ISSN: 1749-0774; 0914-7470; 1749-0774
• DOI: 10.1007/s13577-018-0207-0

Cerebrovascular smooth muscle cell proliferation and migration contribute to hyperplasia in case of cerebrovascular remodeling and stroke. In the present study, we investigated the effects of acetylshikonin, the main ingredient of a Chinese traditional medicine Zicao, on human brain vascular smooth muscle cell (HBVSMCs) proliferation and migration induced by angiotensin II (AngII), and the underlying mechanisms. We found that acetylshikonin treatment significantly inhibited AngII-induced HBVSMCs proliferation and cell cycle transition from G1 to S phase. Wound-healing assay and Transwell assay showed that AngII-induced cell migration and invasion were markedly attenuated by acetylshikonin. In addition, AngII challenge significantly induced Wnt/β-catenin signaling activation, as evidenced by increased β-catenin phosphorylation and nuclear translocation and GSK-3β phosphorylation. However, acetylshikonin treatment inhibited the activation of Wnt/β-catenin signaling. Consequently, western blotting analysis revealed that acetylshikonin effectively reduced the expression of downstream target genes in AngII-treated cells, including c-myc, survivin and cyclin D1, which contributed to the inhibitory effect of acetylshikonin on HBVSMCs proliferation. Further, stimulation with recombinant Wnt3a dramatically reversed acetylshikonin-mediated inhibition of proliferation and cell cycle transition in HBVSMCs. Our study demonstrates that acetylshikonin prevents AngII-induced cerebrovascular smooth muscle cells proliferation and migration through inhibition of Wnt/β-catenin pathway, indicating that acetylshikonin may present a potential option for the treatment of cerebrovascular remodeling.