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14 July 2023 Connexin26 Modulates Radiation-Induced Skin Damage by Regulating Chemokine CCL27 through MAPK Signaling
Rui Tao, Yiwen Mao, Yuan Li, Minqiong Sun, Xiaoping Cao, Ni Chen, Shengmin Xu, Dong Wang, Ye Zhao
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Abstract

Connexin26 (Cx26) plays an important role in ionizing radiation-induced damage, and CC chemokine ligand 27 (CCL27) regulates the skin immune response. However, the relationship between Cx26 and CCL27 in radiation-induced skin damage is unclear. After X-ray irradiation, clonogenic survival and micronucleus formation were assessed in immortalized human keratinocytes (HaCaT). Proteins in the mitogen activated protein kinase (MAPK) signaling pathway and CCL27-related proteins were detected by immunoblotting. HaCaTCx26–/– cells were constructed to verify the effects of Cx26 on CCL27 secretion. A mouse model was established to examine the expression of CCL27 and skin inflammation in vivo. The degree of skin injury induced by 6 MV of X rays was closely related to CCL27. The phosphorylation of ERK, p38 and NF-κB was significantly increased in irradiated cells. The secretion of CCL27 was significantly decreased in HaCaT wild-type cells relative to HaCaTCx26–/– cells. Whereas cell survival fractions decreased, and the micronuclei formation rate increased as a function of increasing X-ray dose in HaCaT cells, the opposite trend occurred in HaCaTCx26–/– cells. Our findings show that Cx26 likely plays a role in the activation of the MAPK and NF-κB/COX-2 signaling pathways and regulates the secretion of CCL27 in keratinocytes after X-ray radiation-induced skin damage.

Rui Tao, Yiwen Mao, Yuan Li, Minqiong Sun, Xiaoping Cao, Ni Chen, Shengmin Xu, Dong Wang, and Ye Zhao "Connexin26 Modulates Radiation-Induced Skin Damage by Regulating Chemokine CCL27 through MAPK Signaling," Radiation Research 200(3), 281-288, (14 July 2023). https://doi.org/10.1667/RADE-20-00085.1
Received: 22 March 2020; Accepted: 19 June 2023; Published: 14 July 2023
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