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

Abstract

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.

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

“…The stimulation of recombinant Wnt3a significantly reversed the acetyl shikonin-mediated inhibition of HBVSMC proliferation and cell cycle transition. Acetyl shikonin inhibits the Wnt/β-catenin pathway to prevent the proliferation and migration of cerebral vascular smooth muscle cells induced by AngII [ 238 ]. Trichoxanthin (TCS) is a biologically active protein extracted and purified from the root tuber of Geranium (a famous Chinese medicinal plant).…”

Protective Effects of Irbesartan, an Angiotensin Receptor Blocker with PPARγ Agonistic Activity, against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats via Modulation of TNFα/Survivin Pathway

“…To our best knowledge, the present study is the first to report the effect of AT1R blockade on downregulation of survivin. However, as AngII is known to increase survivin [ 18 , 45 , 46 , 47 , 48 ], it is not a surprise it is inhibited by AT1R blocker. Moreover, PPARγ activation, which regulates cell proliferation and apoptosis, resulted in decreased survivin expression [ 19 ].…”

WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension

“…Accumulating evidence shows that Wnt/ β ‐catenin signaling exerts a critical role in vascular pathologies. For example, inhibition of Wnt/β‐catenin signaling could attenuate the proliferation and motility of human smooth muscle cells (Cong et al, 2018; Li et al, 2018). A recent study showed that noncanonical Wnt ligand Wnt5a modulates mitochondrial fission–fusion in rat hippocampal neurons (Godoy et al, 2014).…”