TY - JOUR
T1 - 5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Promotes Phenotypic Switching from Dedifferentiated to Differentiated Phenotype via Reactive Oxygen Species and p38 Mitogen-Activated Protein Kinase in Vascular Smooth Muscle Cells
AU - Dan, Juhua
AU - Sun, Xin
AU - Li, Wanlu
AU - Zhang, Yun
AU - Li, Xuesong
AU - Xu, Haobo
AU - Li, Zhitao
AU - Tian, Zhen
AU - Guo, Shuyuan
AU - Yao, Jianting
AU - Gao, Weidong
AU - Tian, Ye
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (81171483 , 81371709 ) and the Foundation of the First Affiliated Hospital Harbin Medical University ( 2014 B04 ). This study was also supported by grants from the Funds for Creative Research Groups of the National Natural Science Foundation of China ( 81121003 ).
Publisher Copyright:
© 2015 World Federation for Ultrasound in Medicine & Biology.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Sonodynamic therapy (SDT) has been found to inhibit in-stent restenosis in animal models. However, the mechanism is not fully elucidated. Here, we investigated the effects of 5-aminolevulinic acid (ALA)-mediated SDT (ALA-SDT) on vascular smooth muscle cells (VSMCs), a cause of restenosis, with a focus on SDT-induced phenotypic switching. Serum-induced dedifferentiated VSMCs were cultured with ALA (1mm, 24h) and exposed to ultrasound (0.8W/cm2) for 5min. Results indicated that ALA-SDT inhibited the migration and proliferation of VSMCs and enhanced the expression of differentiated phenotypic markers in VSMCs. Additionally, ALA-SDT increased intracellular reactive oxygen species accumulation and phosphorylated p38 mitogen-activated protein kinase in VSMCs. Inhibition of reactive oxygen species elevation or p38 mitogen-activated protein kinase activity abolished the expression of smooth muscle 22α (SM22α) in VSMCs induced by ALA-SDT. Taken together, these results suggest that ALA-SDT promotes transformation of the VSMC phenotype from the dedifferentiated to differentiated status via reactive oxygen species and activated p38 mitogen-activated protein kinase.
AB - Sonodynamic therapy (SDT) has been found to inhibit in-stent restenosis in animal models. However, the mechanism is not fully elucidated. Here, we investigated the effects of 5-aminolevulinic acid (ALA)-mediated SDT (ALA-SDT) on vascular smooth muscle cells (VSMCs), a cause of restenosis, with a focus on SDT-induced phenotypic switching. Serum-induced dedifferentiated VSMCs were cultured with ALA (1mm, 24h) and exposed to ultrasound (0.8W/cm2) for 5min. Results indicated that ALA-SDT inhibited the migration and proliferation of VSMCs and enhanced the expression of differentiated phenotypic markers in VSMCs. Additionally, ALA-SDT increased intracellular reactive oxygen species accumulation and phosphorylated p38 mitogen-activated protein kinase in VSMCs. Inhibition of reactive oxygen species elevation or p38 mitogen-activated protein kinase activity abolished the expression of smooth muscle 22α (SM22α) in VSMCs induced by ALA-SDT. Taken together, these results suggest that ALA-SDT promotes transformation of the VSMC phenotype from the dedifferentiated to differentiated status via reactive oxygen species and activated p38 mitogen-activated protein kinase.
KW - 5-Aminolevulinic acid
KW - P38 mitogen-activated protein kinase
KW - Reactive oxygen species
KW - Sonodynamic therapy
KW - Vascular smooth muscle cell
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U2 - 10.1016/j.ultrasmedbio.2014.12.664
DO - 10.1016/j.ultrasmedbio.2014.12.664
M3 - Article
C2 - 25796412
AN - SCOPUS:84929514284
SN - 0301-5629
VL - 41
SP - 1681
EP - 1689
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 6
ER -