title: CCN1, a Pro-Inflammatory Factor, Aggravates Psoriasis Skin Lesions by Promoting Keratinocyte Activation.
abstract: Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Here we demonstrate that CCN1 (also called Cyr61, which is short for cysteine-rich 61), an extracellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod (IMQ)- and IL-23-treated psoriasis-like mice. Then we show that blocking CCN1 function in vivo attenuates epidermal hyperplasia and inflammation in psoriasis-like mice. Further, in primary cultured normal human keratinocytes and HaCaT (human keratinocyte cell line) cells, CCN1 promotes keratinocyte activation, including the proliferation and expression of immune-related molecules. Finally, we observe that integrin α6β1 is the receptor of CCN1 in keratinocytes, and CCN1 stimulation activates the downstream phosphoinositide-3 kinase/Akt/NF-κB signaling pathway. Taken together, our findings reveal that CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix (ECM) protein, our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent target for psoriasis treatment.
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Dermatology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Pinru
authors.initials: P
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Rongfen
authors.initials: R
authors.lastname: Huo
authors.affiliation: Department of Dermatology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Beiqing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tianhang
authors.initials: T
authors.lastname: Zhai
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Baihua
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: ninglixiaoxue57@163.com.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Immunology and Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: ninglixiaoxue57@163.com.
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001707:Biopsy, Needle; D049109:Cell Proliferation; D002478:Cells, Cultured; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D053759:Interleukin-23 / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology*; D011897:Random Allocation; D015398:Signal Transduction
chemical_list: D000634:Aminoquinolines; C491850:CCN1 protein, mouse; D055515:Cysteine-Rich Protein 61; D018836:Inflammation Mediators; D053759:Interleukin-23; D000077271:Imiquimod