title: Epidermal CD147 expression plays a key role in IL-22-induced psoriatic dermatitis.
abstract: Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and terminal differentiation. Interleukin-22 (IL-22) and the transcription factor Stat3 play pivotal roles in the pathogenesis of psoriasis. CD147 is a transmembrane glycosylation protein that belongs to the immunoglobulin superfamily. Our previous studies have shown that CD147 is a marker of high keratinocyte proliferation and poor keratinocyte differentiation as well as a psoriasis susceptibility gene. The current study demonstrates that CD147 is highly expressed in psoriatic skin lesions. Specific CD147 over-expression in the epidermis of K5-promoter transgenic mice promotes imiquimod (IMQ)-induced psoriasis-like inflammation characterized by acanthosis, granular layer loss and inflammatory cell infiltration. We also found that IL-22 increases CD147 transcription in vitro and in vivo and that Stat3 binds directly to the CD147 promoter between positions -854 and -440, suggesting that CD147 expression is up-regulated in patients with psoriasis through Stat3 activation. In addition, CD147 knockdown dramatically blocks IL-22-mediated Stat3 activation as well as IL-22-induced cytokine, chemokine and antimicrobial factor expression. Together, these findings show that CD147 is a novel and key mediator of IL-22-induced psoriatic alterations in the epidermis and might be a therapeutic target in patients with psoriasis.
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: ShengXi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D051926:Basigin / Q000096:biosynthesis* / Q000235:genetics; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000009:adverse effects* / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011565:Psoriasis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D051926:Basigin; D007378:Interleukins; D000097043:Interleukin-22; C497886:BSG protein, human