Pifu-xingbing zhenliaoxue zazhi (Apr 2022)
Expression of the RUNX family in skin lesions from patients with psoriasis vulgaris
Abstract
Objective To explore the expression and distribution of runt-related transcription factor (RUNX) family in lesions of psoriasis vulgaris (PV), and analyze the correlation between its levels and markers of proliferation, apoptosis and immunity. Methods The transcript levels of RUNX1, 2 and 3 were analyzed in normal skin from 14 healthy controls (HC) and lesions from 17 patients with PV by gene array from a published database. The protein levels and distribution of RUNX1, 2, and 3 were examined by immunohistochemistry (IHC) in normal skin from 11 HC and lesions from 11 patients with chronic eczema (CE) and 12 patients with PV. The correlation between RUNX and other genes in the gene array was analyzed by R, and GO enrichment analysis was performed. Results Compared with HC, the transcript levels of RUNX1 were down-regulated (HC: 0.61±0.06, PV: 0.54±0.02, P<0.01), and the levels of RUNX3 were up-regulated in PV lesions (HC: 0.77±0.04, PV: 0.84±0.05, P<0.01), while the expression of RUNX2 showed no differences between the two groups (HC: 0.78±0.05, PV: 0.82±0.04, P=0.18). IHC revealed that RUNX1 was expressed in epidermal keratinocytes and dermal infiltrating inflammatory cells in the skin, while RUNX2 and RUNX3 were more abundant in inflammatory cells. RUNX1 protein levels were down-regulated in the epidermis of CE and PV compared to those in HC (HC: 0.24±0.06, PV: 0.11±0.02, CE: 0.11±0.02, HC vs PV: P<0.01, HC vs CE: P<0.01). Compared with HC and CE, the expression of RUNX2 was higher in epidermis of the PV (HC: 0.02±0.01, PV: 0.04±0.02, CE: 0.02±0.02, HC vs PV: P=0.018, PV vs CE: P=0.019). No difference was found in epidermal expression of RUNX3 among three groups (HC: 0.005±0.004, PV: 0.011±0.016, CE: 0.015±0.020, P=0.861). Correlation and functional analysis suggested that the expression of RUNX1 were related to proliferation and apoptosis markers (BCL2A1, WNT2, WNT7B, WNT8A, WNT9B) and Th17 pathway (IL-17A, IL-17F, IL-17E). The genes positively correlated with RUNX3 were mainly participated in the activation and differentiation of T cells and lymphocytes. The genes negatively correlated with RUNX3 involved in negatively regulating the WNT pathway. RUNX3 was positively correlated with Th1 (STAT4, CXCR3, TNF), Th17 (CCR6, IL-22), Treg (TGFB, IL-10) related markers. Conclusion The expression and distribution pattern of RUNX family is significantly altered in skin lesions from PV patients. RUNX1 and RUNX3 are closely related to the signal pathways of proliferation and apoptosis, T cell immunity (especially Th17 pathways) in psoriatic lesions, and may be involved in the pathogenesis of psoriasis.
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