中华皮肤科杂志 ›› 2026, Vol. 59 ›› Issue (7): 654-661.doi: 10.35541/cjd.20250601

• 论著·光皮肤病学 • 上一篇    下一篇

角质形成细胞谷氨酰胺酶1/氨代谢轴在中波紫外线诱导的急性损伤和银屑病皮肤炎症中的表达研究

宇文天翊1    周子桢1    田竞宇1    陈思涵2    李敏2    张峰源1    顾恒1，2    陈旭1，2   

  1. 1北京协和医学院 中国医学科学院 皮肤病医院 皮肤病研究所，南京  210042；2中国医学科学院北京协和医学院，皮肤病医院江苏省皮肤医学重点实验室，南京  210042
  • 收稿日期:2025-10-29 修回日期:2026-04-08 发布日期:2026-07-03
  • 通讯作者: 陈旭 E-mail:doctor_chx@126.com
  • 基金资助:
    国家自然科学基金（82173438）

Expression of the glutaminase 1/ammonia metabolism axis in keratinocytes in ultraviolet B-induced acute skin injury and psoriatic skin inflammation

Yuwen Tianyi¹, Zhou Zizhen¹, Tian Jingyu¹, Chen Sihan², Li Min², Zhang Fengyuan¹, Gu Heng1,², Chen Xu1,²   

  1. 1Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Nanjing 210042, China; 2Jiangsu Provincial Key Laboratory of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210042, China
  • Received:2025-10-29 Revised:2026-04-08 Published:2026-07-03
  • Contact: Chen Xu E-mail:doctor_chx@126.com
  • Supported by:
    National Natural Science Foundation of China（82173438）

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摘要： 【摘要】 目的 研究角质形成细胞谷氨酰胺酶1（GLS1）在中波紫外线（UVB）诱导的急性损伤和银屑病这两种皮肤炎症损伤模式中的表达调控差异。方法 在基因表达综合数据库（GEO）中选取RNA seq数据集分别分析曝光与非曝光的人原代角质形成细胞和银屑病患者与健康对照正常皮肤组织中GLS1 mRNA的表达。免疫组化检测人体正常曝光皮肤组织、非曝光皮肤组织以及银屑病皮损表皮中GLS1的表达。选取6 ~ 8周龄野生型C57BL/6JGpt小鼠分别进行以下实验：①使用单次UVB照射小鼠脱毛背部，构建UVB急性损伤模型（UVB组）及不照射UVB的对照组，每组4只；②小鼠脱毛背部外用咪喹莫特乳膏构建银屑病样皮炎模型（咪喹莫特组），对照小鼠涂抹凡士林（凡士林组），每组4只。采用qPCR和蛋白质印迹法分别检测每组小鼠皮肤组织中GLS1 mRNA和蛋白的表达；采用氨检测试剂盒和谷氨酸检测试剂盒检测每组小鼠表皮中氨和谷氨酸的含量。结果 GEO数据库分析显示，UVB照射的人原代角质形成细胞中GLS1 mRNA表达水平低于未照射的对照细胞（t = 18.88，P < 0.001）；银屑病患者皮损GLS1 mRNA表达水平低于健康对照（Z = -3.46，P < 0.001）。免疫组化检测显示，正常曝光部位皮肤GLS1表达量低于非曝光部位皮肤（t = 6.25，P = 0.003）；银屑病组皮损GLS1表达量亦低于健康对照组（t = 2.82，P = 0.048）。qPCR检测显示，UVB组小鼠表皮GLS1 mRNA表达水平低于不照射UVB的对照组（t = 4.29，P = 0.005）；咪喹莫特组小鼠亦低于凡士林组（t = 4.22，P = 0.006）。蛋白质印迹检测显示，UVB组和咪喹莫特组小鼠皮损组织中GLS1蛋白表达量同样低于相应的对照组（均P < 0.05）。UVB组小鼠表皮中氨含量为（8.54 ± 1.57） ng/μg，低于不照射UVB的对照组［（18.05 ± 2.41） ng/μg，t = 5.75，P < 0.05］；咪喹莫特组小鼠表皮中氨含量为（8.12 ± 4.79） ng/μg，低于凡士林组［（18.75 ± 2.18） ng/μg，t = 3.52，P < 0.05］。UVB组和咪喹莫特组小鼠表皮中谷氨酸含量与各自对照组比较，差异无统计学意义（均P > 0.05）。结论 角质形成细胞在UVB诱导的急性损伤及银屑病皮损中均表现出谷氨酰胺相关代谢通路下调及GLS1表达下调。

关键词: 银屑病, 角蛋白细胞, 谷氨酰胺酶, 氨, 中波紫外线急性损伤

Abstract: 【Abstract】 Objective To investigate the differences in glutaminase 1 （GLS1） expression in keratinocytes in two inflammatory skin injury models （ultraviolet B ［UVB］-induced acute injury and psoriatic inflammation）. Methods RNA-seq datasets were retrieved from the Gene Expression Omnibus （GEO） database to analyze GLS1 mRNA expression in UVB-exposed and non-UVB-exposed primary human keratinocytes, as well as in psoriatic lesions and normal skin tissues from healthy controls. GLS1 expression was assessed by immunohistochemical analysis in human skin samples, including sun-exposed normal skin tissues, non-sun-exposed normal skin tissues, and psoriatic lesional tissues. Wild-type C57BL/6JGpt mice aged 6 to 8 weeks were used in the following experiments: （1） mouse models of UVB-induced acute skin injury were established by a single exposure to UVB radiation on the shaved dorsal skin （UVB group, n = 4）, with non-irradiated mice serving as controls （n = 4）; （2） mouse models of psoriasis-like skin inflammation were established by topical application of imiquimod cream to the depilated dorsal skin （imiquimod group, n = 4）, with Vaseline-treated mice serving as controls （n = 4）. GLS1 mRNA and protein expression levels in mouse skin were measured by quantitative PCR and Western blot analysis, respectively. Epidermal ammonia and glutamate levels were measured using corresponding assay kits. Results GEO database analysis revealed that GLS1 mRNA expression was significantly reduced in UVB-exposed primary human keratinocytes compared with non-exposed control cells （t = 18.88, P < 0.001）, and also significantly decreased in psoriatic lesions compared with normal skin tissues from healthy controls （Z = -3.46, P < 0.001）. Immunohistochemical analysis showed that GLS1 expression was significantly lower in sun-exposed normal skin tissues than in non-exposed skin tissues （t = 6.25, P = 0.003）, and was also significantly reduced in psoriatic lesions compared with normal skin tissues from healthy controls （t = 2.82, P = 0.048）. qPCR showed that GLS1 mRNA expression in mouse skin was significantly lower in the UVB group than in the control group （t = 4.29, P = 0.005）, as well as in the imiquimod group than in the Vaseline group （t = 4.22, P = 0.006）. Western blot analysis further confirmed that GLS1 protein expression was significantly reduced in the UVB group and the imiquimod group compared with their respective controls （both P < 0.05）. Epidermal ammonia levels were significantly lower in the UVB group （［8.54 ± 1.57］ ng/μg vs. ［18.05 ± 2.41］ ng/μg, t = 5.75, P < 0.05） and in the imiquimod group （［8.12 ± 4.79］ ng/μg vs. ［18.75 ± 2.18］ ng/μg, t = 3.52, P < 0.05） compared with their respective controls. No significant differences in epidermal glutamate levels were observed between either the UVB or imiquimod group and their respective controls （both P > 0.05）. Conclusion GLS1 expression and glutamine-related metabolic pathways were downregulated in keratinocytes in both UVB-induced acute skin injury and psoriasis-like lesions.

Key words: Psoriasis, Keratinocytes, Glutaminase, Ammonia, Ultraviolet B-induced acute injury

引用本文

宇文天翊 周子桢 田竞宇 陈思涵 李敏 张峰源 顾恒 陈旭. 角质形成细胞谷氨酰胺酶1/氨代谢轴在中波紫外线诱导的急性损伤和银屑病皮肤炎症中的表达研究[J]. 中华皮肤科杂志, 2026,59(7):654-661. doi:10.35541/cjd.20250601

Yuwen Tianyi¹, Zhou Zizhen¹, Tian Jingyu¹, Chen Sihan², Li Min², Zhang Fengyuan¹, Gu Heng, ², Chen Xu, ². Expression of the glutaminase 1/ammonia metabolism axis in keratinocytes in ultraviolet B-induced acute skin injury and psoriatic skin inflammation[J]. Chinese Journal of Dermatology, 2026, 59(7): 654-661.doi:10.35541/cjd.20250601