Sphingosylphosphorylcholine (SPC), a Causative Factor of SPC-Induced Vascular Smooth Muscle Cells Contraction, Is Taken Up via Endocytosis

Cells. 2023 Jan 9;12(2):265. doi: 10.3390/cells12020265.


The reaction field of abnormal vascular contraction induced by sphingosylphosphorylcholine (SPC) and the action point of SPC around the plasma membranes remain unknown. However, we found in a previous study that fisetin prevents SPC-induced vascular smooth muscle cells contraction, while the mechanism remains unknown. Therefore, in this study, we aimed to address the action point of SPC around the plasma membranes and the involvement of fisetin. We focused on microdomains and evaluated their markers flotillin-1 and caveolin-1 and the localization of SPC to investigate their action point. The results showed that microdomains of vascular smooth muscle cells were not involved in SPC-induced contraction. However, we found that after SPC had been affected on the plasma membrane, cells took up SPC via endocytosis. Moreover, SPC remained in the cells and did not undergo transcytosis, and SPC-induced contracting cells produced exosomes. These phenomena were similar to those observed in fisetin-treated cells. Thus, we speculated that, although not involved in the reaction field of SPC-induced contractions, the microdomain induced the endocytosis of SPCs, and fisetin prevented the contractions by directly targeting vascular smooth muscle cells. Notably, this preventive mechanism involves the cellular uptake of SPC via endocytosis.

Keywords: endocytosis; exocytosis; fisetin; microdomains; sphingosylphosphorylcholine; vascular smooth muscle contraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endocytosis
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular* / metabolism
  • rho-Associated Kinases* / metabolism


  • rho-Associated Kinases
  • sphingosine phosphorylcholine

Grant support

This research was funded by JSPS KAKENHI (grant numbers 20H02936 and 21J13092) and the NICA Fellows program (2021). The funding agencies had no role in the study design, data collection analysis, decision to publish, or preparation of the manuscript.