Mechanism of Cadmium-Induced Hyaluronan Synthesis in Vascular Endothelial Cells Unveiled: Discovery of Disruption in Glycan Synthesis by Toxic Substances

A research team led by Ms. Misaki Shirai (JSPS Research Fellow), Dr. Takato Hara, and Dr. Chika Yamamoto from the Department of Environmental Health Science, Faculty of Pharmaceutical Sciences, Toho University, has revealed that cadmium, a toxic heavy metal, increases the synthesis of hyaluronan in vascular endothelial cells. Their study has also identified that this process is mediated by the induction of hyaluronan synthase 3 (HAS3) expression.
In Japan, cadmium is well known as the causative agent of Itai-itai disease, and numerous epidemiological studies have highlighted its role as a risk factor for atherosclerosis. This study provides new insights into the toxic mechanisms of cadmium, demonstrating that it accelerates the progression of atherosclerosis by increasing hyaluronan synthesis.
This research was published online in the journal Toxicology on January 20, 2025.

From left: Dr. Takato Hara, Ms. Misaki Shirai, Dr. Chika Yamamoto

Key Points:

Cadmium increases hyaluronan synthesis in vascular endothelial cells.
The increase in hyaluronan synthesis is mediated by the induction of HAS3 expression, triggered by the activation of the JNK–c-Jun pathway due to cadmium exposure.
Disruption of HAS3 expression balance in vascular endothelial cells due to cadmium exposure may accelerate the progression of inflammatory vascular diseases, including atherosclerosis.

graphical abstract of this study

Journal
Toxicology (January 20, 2025) Vol. 511, Article 154062

Title:
Cadmium promotes hyaluronan synthesis by inducing hyaluronan synthase 3 expression in cultured vascular endothelial cells via the c-Jun N-terminal kinase–c-Jun pathway

Authors:
Misaki Shirai, Takato Hara, Toshiyuki Kaji, Chika Yamamoto* (*Corresponding Author)

DOI: 10.1016/j.tox.2025.154062

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