Jiaxin Zong1, Jieyi Cheng2,3, Yuanfeng Fu1, Jing Song2, Weisong Pan4, Li Yang2, Ting Zhang1, Mingmei Zhou2. 1. Murad Research Center for Modernized Chinese Medicine, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 2. Center for Chinese Medicine Therapy and Systems Biology, Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 3. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 4. Guangzhou Institute for Drug Control, Guangzhou, China.
Abstract
BACKGROUND: The imiquimod (IMQ)-induced psoriasis mouse model has been used as a model for pathogenic mechanism research, and methotrexate (MTX) is widely employed to treat various clinical manifestations of psoriasis. We explored the underlying pathogenesis of psoriasis and the treatment mechanism of the conventional drugs from the metabolic perspective of the psoriasis mouse model. METHODS: Male BALB/c mice were smeared IMQ for 7 days to induce treatment-resistant psoriasis and intragastrically administered 1 mg/kg MTX. We evaluated inflammation of psoriasis-like lesions and therapeutic effects of MTX based on histological changes and immunohistochemistry. Based on gas chromatography-mass spectrometer detection of serum samples, a comprehensive metabolomics analysis was carried out to identify alterations of metabolites. RESULTS: It was found that MTX ameliorated psoriatic lesions (representative erythema, scaling, and thickening) by inhibiting proliferation and differentiation of keratinocytes. Using multivariate statistical analysis to process metabolomics data, the results displayed alterations in serum metabolites among mice of the control group, IMQ group, and MTX group. Compared with group, psoriasis mice had the higher level of d-galactose and lower expression of myo-inositol, 9,12-octadecadienoic acid, and cholesterol. In contrast with the model set, serum levels of glycine, pyrrolidone carboxylic acid, d-galactose, and d-mannose were significantly decreased in the MTX group. CONCLUSION: The differential metabolites, reflecting the perturbation in the pathways of inositol phosphate metabolism; galactose metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and glutathione metabolism, may lead to the pathogenesis of psoriasis, and they are also related to the pharmacological treatment effect of MTX on psoriasis. This study established the foundation for further research on the mechanism and therapeutic targets of psoriasis.
BACKGROUND: The imiquimod (IMQ)-induced psoriasis mouse model has been used as a model for pathogenic mechanism research, and methotrexate (MTX) is widely employed to treat various clinical manifestations of psoriasis. We explored the underlying pathogenesis of psoriasis and the treatment mechanism of the conventional drugs from the metabolic perspective of the psoriasis mouse model. METHODS: Male BALB/c mice were smeared IMQ for 7 days to induce treatment-resistant psoriasis and intragastrically administered 1 mg/kg MTX. We evaluated inflammation of psoriasis-like lesions and therapeutic effects of MTX based on histological changes and immunohistochemistry. Based on gas chromatography-mass spectrometer detection of serum samples, a comprehensive metabolomics analysis was carried out to identify alterations of metabolites. RESULTS: It was found that MTX ameliorated psoriatic lesions (representative erythema, scaling, and thickening) by inhibiting proliferation and differentiation of keratinocytes. Using multivariate statistical analysis to process metabolomics data, the results displayed alterations in serum metabolites among mice of the control group, IMQ group, and MTX group. Compared with group, psoriasis mice had the higher level of d-galactose and lower expression of myo-inositol, 9,12-octadecadienoic acid, and cholesterol. In contrast with the model set, serum levels of glycine, pyrrolidone carboxylic acid, d-galactose, and d-mannose were significantly decreased in the MTX group. CONCLUSION: The differential metabolites, reflecting the perturbation in the pathways of inositol phosphate metabolism; galactose metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and glutathione metabolism, may lead to the pathogenesis of psoriasis, and they are also related to the pharmacological treatment effect of MTX on psoriasis. This study established the foundation for further research on the mechanism and therapeutic targets of psoriasis.
Authors: James F Markworth; Gunveen Kaur; Eliza G Miller; Amy E Larsen; Andrew J Sinclair; Krishna Rao Maddipati; David Cameron-Smith Journal: FASEB J Date: 2016-07-26 Impact factor: 5.191
Authors: Alexander V Sorokin; Anthony F Domenichiello; Amit K Dey; Zhi-Xin Yuan; Aditya Goyal; Shawn M Rose; Martin P Playford; Christopher E Ramsden; Nehal N Mehta Journal: J Invest Dermatol Date: 2018-02-15 Impact factor: 8.551
Authors: Kondala R Atkuri; John J Mantovani; Leonard A Herzenberg; Leonore A Herzenberg Journal: Curr Opin Pharmacol Date: 2007-06-29 Impact factor: 5.547