Keratinocyte-Specific CCN1 Modulation Driven Regulation of Keratinocyte Proliferation and Inflammation in Psoriasis

Abstract

Abstract Background: Psoriasis is a chronic autoimmune disease characterized by the hyperproliferation of keratinocytes and inflammatory cell infiltration. CCN1 is a matricellular protein that plays a crucial role in cell proliferation, differentiation, and adhesion, which are accepted as psoriasis-relevant. Objective: Our study evaluated the function of CCN1 in psoriasis treatment using keratinocyte-specific Ccn1 transgenic mice. Methods and Results: We constructed keratinocyte tissue-specific Ccn1 transgenic mice and induced a psoriasis model with imiquimod (IMQ). The results exhibited that, compared to the psoriatic model group, the keratinocyte-specific ablation of Ccn1 ameliorated IMQ-induced psoriasis-like skin lesions in mice. Furthermore, the downregulation of PCNA+ cells, NF-kB P50+, F4/80+ macrophage, CD3+ T lymphocytes, and pSTAT3 was confirmed by immunohistochemical staining in the epidermis of psoriatic lesions. Keratinocyte-specific Ccn1 overexpression also increased inflammation in mice after exposure to imiquimod, exhibiting more pronounced red and scaly plaques, epidermal hyperproliferation, and abnormal differentiation of keratinocytes. Thus, targeting CCN1 could broadly improve psoriasis treatment outcomes. Conclusion: Overall, epidermal-specific CCN1 exerts a key player in keratinocyte proliferation and immunoinflammation in the psoriasis setting. Our study yields valuable insights into the pathogenesis and potential treatment of the disease.