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Published on: March 29, 2024
Syndecan-4 regulates platelet-derived growth factor-mediated MAP kinase activation by altering intracellular reactive
Jungyean Kim1, Jung-hyun Lee, Hey Sun Park
1Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul 120-750, Republic of Korea.
Abstract:
The cell adhesion receptor, syndecan-4, regulates cellular interactions with both the extracellular matrix and soluble ligands. Accumulating evidence also suggests that cell adhesion is involved in generating reactive oxygen species (ROS). Here, we investigated the role of syndecan-4 in regulating growth factor-induced ROS generation. Rat embryo fibroblasts (REFs) overexpressing syndecan-4 exhibited increased ROS levels compared to control cells. Expression of the non-phagocytic NADH oxidase component Nox1 was increased in syndecan-4-overexpressing REFs and syndecan-4-mediated ROS generation was diminished when levels of Nox1 were knocked-down with small inhibitory RNAs. In addition, syndecan-4 enhanced platelet-derived growth factor (PDGF)-induced MAP kinase activity in parallel with ROS generation. Collectively, these data suggest that syndecan-4 regulates PDGF-induced MAP kinase activation by altering ROS generation.
Insights
Syndecan-4 increases reactive oxygen species (ROS) by regulating the NADH oxidase component Nox1. This mechanism mediates platelet-derived growth factor-induced MAP kinase activation in cells.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Syndecan-4 is a cell adhesion receptor involved in cellular interactions.
- Cell adhesion is increasingly linked to the generation of reactive oxygen species (ROS).
Purpose of the Study:
- To investigate the role of syndecan-4 in regulating growth factor-induced ROS generation.
- To understand the molecular mechanisms by which syndecan-4 influences ROS production and downstream signaling.
Main Methods:
- Overexpression of syndecan-4 in rat embryo fibroblasts (REFs).
- Knockdown of Nox1 expression using small inhibitory RNAs.
- Measurement of ROS levels.
- Assessment of MAP kinase activity.
Main Results:
- Syndecan-4 overexpression led to increased ROS levels in REFs.
- Nox1 expression was upregulated in syndecan-4-overexpressing cells.
- Knockdown of Nox1 diminished syndecan-4-mediated ROS generation.
- Syndecan-4 enhanced platelet-derived growth factor (PDGF)-induced MAP kinase activity, correlating with ROS generation.
Conclusions:
- Syndecan-4 plays a key role in regulating ROS generation.
- Syndecan-4-mediated ROS production involves the NADH oxidase component Nox1.
- Syndecan-4 regulates PDGF-induced MAP kinase activation through modulation of ROS generation.
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