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CCN1 (also termed CYR61 or cysteine\u2010rich angiogenic inducer 61) is an extracellular matrix\u2010associated protein that is involved in multiple physiological functions. In psoriasis, we recently demonstrated that the overexpression of CCN1 promoted keratinocyte proliferation and activation. Furthermore, CCN1 was highly expressed in psoriatic skin lesions from psoriasis vulgaris patients. Here, we dissect the underlying molecular mechanism in imiquimod (IMQ) and interleukin (IL)\u201023\u2010induced psoriasis\u2010like models. Our results demonstrate that CCN1 can significantly upregulate IL\u201036 production in the murine skin of IMQ and IL\u201023\u2010induced psoriasis\u2010like models. Injection of CCN1\u2010neutralizing antibody improved epidermal acanthosis and significantly reduced IL\u201036 production in vivo. These results suggest that CCN1 can be a critical upstream pro\u2010inflammatory factor in psoriasis. In primary normal human epidermal keratinocytes, we demonstrated that CCN1 can selectively induced the production of IL\u201036\u03b1 and IL\u201036\u03b3 through the activation of the protein kinase B (AKT)\/nuclear factor kappa light chain enhancer of activated B cells (NF\u2010\u03baB) and extracellular\u2010regulated kinase (ERK)\/CCAAT\/enhancer binding protein \u03b2 (CEBP\u03b2) signaling pathways via integrin receptor \u03b16\u03b21 in vitro. Our results suggest that targeting CCN1 can be a potential therapeutic strategy for psoriasis.<\/jats:p>","DOI":"10.1111\/1346-8138.16611","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T03:16:56Z","timestamp":1668482216000},"page":"337-348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>CCN1<\/scp> upregulates <scp>IL<\/scp>\u201036 via <scp>AKT<\/scp>\/<scp>NF\u2010\u03baB<\/scp> and <scp>ERK<\/scp>\/<scp>CEBP \u03b2<\/scp>\u2010mediated signaling pathways in psoriasis\u2010like models"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-4154","authenticated-orcid":false,"given":"Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory of Tongren Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai 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and Microbiology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichuan","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology &amp; Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology &amp; Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongfen","family":"Huo","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology &amp; Department of Immunology and Microbiology Shanghai Jiao Tong University School of Medicine  Shanghai 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