Abstract：
Radiation-induced cutaneous ulcers are a challenging medical problem for patients receiving radiation therapy. The inhibition of cell senescence has been suggested as a prospective strategy to prevent radiation ulcers. However, there is no effective treatment for senescent cells in radiation ulcers. In this study, we investigated whether zileuton alleviated radiation-induced cutaneous ulcer by focusing on cell senescence. We demonstrate increased cell senescence and senescence-associated secretory phenotype (SASP) in irradiated dermal fibroblasts and skin tissue. The SASP secreted from senescent cells induces senescence in adjacent cells. In addition, 5-lipoxygenase (5-LO) expression increased in irradiated dermal fibroblasts and skin tissue, and SASP and cell senescence were regulated by 5-LO through p38 phosphorylation. Finally, the inhibition of 5-LO following treatment with zileuton inhibited SASP and mitigated radiation ulcers in animal models. Our results demonstrate that inhibition of SASP from senescent cells by zileuton can effectively mitigate radiation-induced cutaneous ulcers, indicating that inhibition of 5-LO might be a viable strategy for patients with this condition.
摘要：
辐射诱发的皮肤溃疡对于接受放射治疗的患者来说是一个具有挑战性的医学问题。抑制细胞衰老已被建议作为预防放射性溃疡的前瞻性策略。然而,对于放射性溃疡中的衰老细胞没有有效的治疗方法。在这项研究中,我们研究齐替通是否通过关注细胞衰老来缓解辐射诱导的皮肤溃疡。我们证明了受辐照的真皮成纤维细胞和皮肤组织中细胞衰老和衰老相关分泌表型（SASP）的增加。从衰老细胞分泌的SASP诱导邻近细胞的衰老。此外,5-脂氧合酶（5-LO）在照射真皮成纤维细胞和皮肤组织中的表达增加，5-LO通过p38磷酸化调节SASP和细胞衰老。最后,在动物模型中，用齐留通治疗后5-LO的抑制抑制SASP并减轻放射性溃疡。我们的结果表明，zileuton抑制SASP从衰老细胞可以有效地减轻辐射诱导的皮肤溃疡，表明抑制5-LO可能是患有这种疾病的患者的可行策略。
