动物造模,银屑病模型 z-bio 2023-09-13 1020

　　(1) Animal models related to the Stat3 pathway: Sano S et al. continuously activated the Star3 pathway by inserting the KRT5 promoter into basal keratinocytes, leading to spontaneous or psoriatic skin lesions in response to external damage, such as keratinocyte proliferation (acanthosis) accompanied by loss of granular layer and incomplete keratinization, significant dilation of blood vessels, and infiltration of inflammatory cells mainly composed of lymphocytes and neutrophils. Inhibiting the activation of Stat3 can reverse the occurrence of skin lesions. Other similar models include inserting KRT14 to overexpress IL-20 and IL-6 in basal cells, inserting KRT-5 to overexpress leptin in basal cells, and so on. Relatively speaking, the first model is better. However, this type of model has some aspects that are different from human psoriasis, such as hair loss, hair abnormalities, growth retardation, corneal damage, etc.

　　(2) TGF- β Related animal models: Liu et al. upregulated TGF in basal layer cells of adult mice under the control of trans tetracycline regulatory activating factors- β The expression of 1 induces keratinocyte proliferation, dermal fibrosis, and inflammatory infiltration, while also not growing hair. Gordon et al. overexpressed TGF in mouse basal layer cells using the KRT5 promoter- β 1. This leads to a significant phenotype of psoriasis, such as keratinization with incomplete keratinization, epidermal hyperplasia, scattered infiltration of monocytes within the epidermis, formation of subcutaneous pustules, and significant vascular proliferation. Additionally, TGF- β Another member of the superfamily, bone morphogenetic protein 6 (BMP-6), can also lead to intense epidermal proliferation and incomplete keratinization if its expression is reduced in basal cells.

　　(3) β 1. Integrin transgenic mouse model: β Integrins are usually limited in expression in basal layer cells of the epidermis, when expressed in cells above the basal layer β At the time of 1 integrin, inflammation appeared in the epidermis of mice 6 weeks later, with several pathological features of psoriasis: inflammation infiltration characterized by incomplete keratinization and neutrophil pustules. CD8+T cell infiltration mainly appeared in the epidermis, while CD4+T cells appeared in the dermis.

　　(4) As one of the heparin binding members, bimodulin belongs to the epidermal growth factor family and is associated with other non heparin binding factors (TNF- α There are distinct biochemical and biological characteristics. If bimodulin is expressed in basal cells of a mouse model, severe inflammatory skin lesions such as significant scaling, hair loss, papillary epidermal growth, neutrophils, lymphocyte infiltration, and telangiectasia in the dermis will occur. And TNF- α When expressed in the basal layer cells of the skin, only focal thickening of the skin occurs and hair growth is hindered.