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Banzhilian Formula alleviates psoriasis like lesions via the LCN2/MMP-9 axis based on transcriptome analysis

ABSTRACT: Oral Banzhilian Formula (BZLF) is effective in the clinical treatment of psoriasis. However, the effectiveness and mechanism of different drug delivery routes deserve further study. In this study, we externally applied BZLF to the skin lesions in an IMQ-induced psoriasis mice model, and found that BZLF alleviated the psoriasis-like skin lesions, while inhibiting the expression of Ki67 and inflammatory factors (Il17a, Tnf-α, S100a7 and Cxcl1) in the skin lesions. Finally, through transcriptome sequencing combined with bioinformatics and other methods, it was found that the mechanism of action of BZLF against psoriasis is achieved by down-regulating the LCN2/MMP-9 axis. Overall, this study elucidates the effectiveness and mechanism of external application of BZLF in the treatment of psoriasis, and provided a new approach and basis for clinical application.

ORGANISM(S): Mus musculus

PROVIDER: GSE223468 | GEO | 2023/03/29

REPOSITORIES: GEO

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Project description:Atopic dermatitis (AD) is a common disease, with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in lack of specific treatments. The prevailing view is that AD is a biphasic, T-cell polarized disease, with Th2 predominating acute AD, and a switch to Th1 characterizing chronic disease. Identification of factors that participate in onset of lesions and maintenance of chronic lesions is critical for development of targeted therapeutics. We performed global genomic, molecular and cellular profiling of paired non-lesional, acute, and chronic skin biopsies from ten AD patients. Onset of acute lesions is associated with a striking increase in a subset of terminal differentiation proteins, specifically the IL-22-modulated S100A7-9. Correspondingly, acute disease is associated with significant increases in gene expression levels of the major Th22- (IL-22) and Th2- (IL-4, IL-31) cytokines and Th17-regulated genes (CCL20, PI3/Elafin), without significant changes in IL-17. A lesser induction of Th1- (IFNγ, MX-1, CXCL9-11) associated genes was detected in acute disease. Chronic skin lesions are characterized by significantly intensified activation of Th22, Th2 and Th1. Our data establish increased expression of S100A7-9 and other epidermal genes at onset of acute AD, with parallel activation of Th2 and Th22 cytokines. Our findings suggest an absence of switch mechanism in chronic disease and instead indicate that progression to chronic lesions is associated with intensified activation of immune axes that initiate onset of acute lesions, particularly Th22 and Th2. This alters the prevailing view of pathogenesis, with important therapeutic implications. Acute, chronic, and non-lesional skin samples were collected from ten patients with moderate-to-severe AD that met our inclusion criteria, under an institutional review board–approved protocol. The following criteria were employed to define acute AD and distinguish true acute from “acute on chronic” skin lesions: a) new lesions of <72 hours duration, as previously defined;14 b) lack of skin lichenification; c) lack of regenerative hyperplasia, as defined by epidermal thickness ≤150μ [hematoxylin and eosin (H&E)] and basal or confluent supra-basal Keratin 16 (K16) positivity. No systemic or topical treatments were allowed for ≥4 weeks prior to biopsies. Biopsy specimens were frozen in optimal cutting temperature (OCT) for immunohistochemistry (IHC) and liquid nitrogen for RNA extraction.

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Banzhilian Formula alleviates psoriasis like lesions via the LCN2/MMP-9 axis based on transcriptome analysis

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