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The Involvement of SDF-1α/CXCR4 Axis in Radiation-Induced Acute Injury and Fibrosis of Skin

The Involvement of SDF-1α/CXCR4 Axis in Radiation-Induced Acute Injury and Fibrosis of Skin

Jinming Cao, Wei Zhu, Daojiang Yu, Lu Pan, Li Zhong, Yuji Xiao, Yiying Gao, Yang Jiao, Qi Zhang, Jiang Ji, Hongying Yang, Shuyu Zhang, Jianping Cao

Radiat Res. 2019 Aug;192(4):410-421.

PMID: 31390312

Abstract:

Radiation-induced acute skin injury and consequent fibrosis are common complications of cancer radiotherapy and radiation accidents. Stromal cell-derived factor-1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4) have been shown to be involved in multiple cellular events. However, the role of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin has not been reported. In this study, we found that the expression of SDF-1α and CXCR4 was significantly increased in irradiated skin tissues of humans, monkeys and rats, compared to their nonirradiated counterparts. Mice with keratinocyte-specific ablation of CXCR4 showed less severe skin damage than wild-type mice after receiving a 35 Gy dose of radiation. Consistently, subcutaneous injection of AMD3100, an FDA approved SDF-1α/CXCR4 inhibitor, attenuated skin injury and fibrosis induced by exposure to radiation in a rat model. Mechanically, the SDF-1α/CXCR4 axis promotes pro-fibrotic TGF-b/Smad signaling through the PI3K-MAPK signaling cascade in human keratinocyte HaCaT cells and skin fibroblast WS1 cells. AMD3100 inhibited Smad2 nuclear translocation and transcriptional activity of Smad2/3 induced by radiation, which suppressed the pro-fibrotic TGF-b/Smad signaling pathway activated by exposure. Taken together, these findings demonstrate the involvement of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin, and indicate that AMD3100 would be an effective countermeasure against these diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413120	SDF-1 beta from rat			Price

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