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Heavy ion radiation induces pyroptosis in skin keratinocytes through a mitogen-activated protein kinase signaling

Zhiqiang Zhang¹, Haoxiang Wang¹, Yumeng Huang¹

¹School of Basic Medical Sciences, Anhui Medical University, Anhui, China.

International Journal of Radiation Biology

|September 23, 2025

Abstract

Purpose:

To elucidate the mechanisms underlying pyroptosis in skin due to heavy ion radiation.

Materials And Methods:

Human keratinocytes (HaCaT cells) were irradiated with different doses of X-rays and ¹²C ions. Clonogenic survival, CCK-8 cell proliferation, and micronucleus assays were performed to assess the radiosensitivity of HaCaT cells. The pyroptosis-related, inflammation-related, and MAPK/NF-κB signaling pathway proteins were detected by Western-blotting.

Results:

¹²C ion radiation caused more severe damage to HaCaT cells than X-rays. The former induced pyroptosis in the HaCaT cells in a dose-dependent manner. Heavy ion-induced pyroptosis was activated by the Caspase-4/Caspase-5/Gasdermin D (GSDMD) pathway, which was regulated by the MAPK/NF-κB signaling pathway.

Conclusions:

¹²C ion irradiation induced pyroptosis in human keratinocytes by a non-classical pathway via the activation of MAPK/NF-κB signaling pathway. The findings may be used to guide further research on targeted interventions to reduce skin damage and optimize treatment strategies in the future.

Keywords:

Heavy ion radiation MAPK/NF-κB signaling pathway pyroptosis radiation-induced skin injury

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