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