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  2. Transglutaminase 3 Attenuates Skin Inflammation in Psoriasis by Inhibiting NF-κB Activation through phosphorylated STAT3-TET3 Signaling

Transglutaminase 3 Attenuates Skin Inflammation in Psoriasis by Inhibiting NF-κB Activation through phosphorylated STAT3-TET3 Signaling

  • J Invest Dermatol. 2022 May 8;S0022-202X(22)00374-8. doi: 10.1016/j.jid.2022.03.035.
Shiqi Ling 1 Beilei Xu 1 Yang Luo 1 Xiaokai Fang 1 Xiaochun Liu 1 Ao Wang 1 Yuan Zhou 1 Shan Zhang 1 Wenkai Zong 2 Wei Li 3 Xu Yao 4
Affiliations

Affiliations

  • 1 Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
  • 2 Department of Dermatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
  • 3 Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
  • 4 Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China. Electronic address: dryao_xu@126.com.
Abstract

Transglutaminase 3 (TGM3) protects against skin inflammation in psoriasis, but the precise role and mechanism of action of TGM3 in the pathogenesis of psoriasis remain unclear. In this study, we show that TGM3 expression was increased in the skin lesions of patients with psoriasis and a mouse model of imiquimod-induced psoriatic dermatitis. TGM3 overexpression decreased the production of proinflammatory factors in cultured primary keratinocytes stimulated with psoriasis-related cytokines. TGM3 inhibited the phosphorylation of signal transducer and activator of transcription 3 and the recruitment of ten-eleven translocation 3 to the p65 gene promoter, resulting in decreased promoter demethylation and subsequent suppression of proinflammatory cytokine/chemokine production. TGM3-induced inhibition of phosphorylated p65 might also decrease ten-eleven translocation 3 expression. Moreover, topical application of Tgm3-specific small interfering RNA or the pan-transglutaminase inhibitor cysteamine exacerbated skin inflammation in mice with imiquimod-induced psoriatic dermatitis. Our study revealed an epigenetic pathway mediated by the interaction between TGM3 and ten-eleven translocation 3 in keratinocytes for regulation of skin inflammation in psoriasis, providing a potential target for psoriasis treatment.

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