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

Juhua Dan, Xin Sun, Wanlu Li, Yun Zhang, Xuesong Li, Haobo Xu, Zhitao Li, Zhen Tian, Shuyuan Guo, Jianting Yao, Weidong Gao, Ye Tian

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1681-1689
Number of pages9
JournalUltrasound in Medicine and Biology
Volume41
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • 5-Aminolevulinic acid
  • P38 mitogen-activated protein kinase
  • Reactive oxygen species
  • Sonodynamic therapy
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Biophysics
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics

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