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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.
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.
Human skin has long been known as a protective organ, acting as a mechanical barrier towards the external environment. More recent is the acquisition that in addition to this fundamental role, the complex architecture of the skin hosts a variety of immune and non-immune cells playing preeminent roles in immunological processes aimed at blocking infections, tumor progression and migration, and elimination of xenobiotics. On the other hand, dysregulated or excessive immunological response into the skin leads to autoimmune reactions culminating in a variety of skin pathological manifestations. Among them is psoriasis, a multifactorial, immune-mediated disease with a strong genetic basis. Psoriasis affects 2–3% of the population; it is associated with cardiovascular comorbidities, and in up to 30% of the cases, with psoriatic arthritis. The pathogenesis of psoriasis is due to the complex interplay between the genetic background of the patient, environmental factors, and both innate and adaptive responses. Moreover, an autoimmune component and the comprehension of the mechanisms linking chronic skin inflammation with systemic and joint manifestations in psoriatic patients is still a major challenge. The understanding of these mechanisms may offer a valuable chance to find targetable molecules to treat the disease and prevent its progression to severe systemic conditions.
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