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Original Articles

Reactive sulfur species inhibit the migration of PDGF-treated vascular smooth muscle cells by blocking the reactive oxygen species-regulated Akt signaling pathway

, ORCID Icon, &
Pages 186-197 | Received 23 Nov 2020, Accepted 03 Feb 2021, Published online: 01 Mar 2021
 

Abstract

Vascular smooth muscle cell (VSMC) migration contributes to vascular remodeling after injury, whereas oxidative stress generated through dysfunctional redox homeostasis induces hypermigration, leading to arteriosclerosis. Platelet-derived growth factor (PDGF)-induced reactive oxygen species (ROS) serve as intracellular signaling molecules in VSMCs. Reactive sulfur species (RSS) may serve as a biological defense system because of the antioxidative properties of highly nucleophilic sulfane sulfur. However, insufficient information is available on its function in PDGF-induced VSMC migration. Here we show that PDGF significantly increased the levels of intracellular sulfane sulfur and that intracellular sulfane sulfur donors, donor 5a and Na2S4, inhibited the increase in ROS levels in PDGF-treated VSMCs and inhibited their migration. Consistent with the migration results, sulfane sulfur donors inhibited Akt phosphorylation, a downstream signaling molecule in the PDGF cascade, without affecting the autophosphorylation of PDGF receptor-β. Further, sulfane sulfur donors inhibited vinculin and paxillin recruitment to the leading edge of VSMCs in response to PDGF to decrease focal adhesion formation. These findings suggest that RSS are required for PDGF-stimulated VSMC migration through the regulation of the ROS-regulated Akt pathway, which may contribute to focal adhesion formation. Our findings provide insight into RSS as novel regulators of vascular redox homeostasis.

Acknowledgments

The authors thank Mayu Watanabe for technical assistance and Enago (www.enago.jp) for editing a draft of this manuscript.

Author contributions

T.A. conceived and designed the research; S.I., T.A., and H.F. performed the experiments; S.I., T.A., and H.F. analyzed the data; S.I. and T.A. interpreted the results of the experiments; S.I. and T.A. prepared the figures; S.I. drafted the manuscript; T.A. edited and revised the manuscript; S.N. supervised; and S.I., T.A., H.F, and S.N. approved the final version of the manuscript.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by JSPS KAKENHI Grant Number 18K08115 (to T.A.) and Takeda Science Foundation (to T.A.).

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