by Toho University

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. Credit: Dr. Chika Yamamoto

A research team 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 is published online in the journal Toxicology. The team was 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.

Key points include:

• 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.

More information: Misaki Shirai et al, 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, Toxicology (2025). DOI: 10.1016/j.tox.2025.154062

Provided by Toho University