Abstract Background Psoriasis is characterized by chronic inflammatory dermatosis, and the pathogenesis of psoriasis is associated with mesenchymal stem cells ( MSC s) and deregulation of the expression of miR‐31. This study aimed to clarify the function of miR‐31 in dermal MSC s ( DMSC s) in the pathogenesis of psoriasis. Methods The expression of miR‐31 was assayed by a microarray and that of target genes of miR‐31 was tested by quantitative PCR . Results The expression of miR‐31 in the psoriasis group was 0.2677 folds that of the control group. The expression of EMP 1 and EIG 121L genes, whose products are located on the cell membrane, in the psoriasis group was 4.095579 and 5.367017 folds that in the control group, respectively. The expression of GRB 10 , PTPN 14 , QKI , RNF 144B , and TACC 2 genes, whose products are located in the cytoplasm, in the psoriasis group was 1.440428, 1.198335, 1.737285, 7.379546, and 1.531947 folds that of the control. The expression of PRELP , whose products are secreted in the extracellular space, in the psoriasis group was 1.351684 folds that of the control. The expression of RBMS 1 , KHDRBS 3 , and SATB 2 , whose products play a role in the nucleus, in the psoriasis group was 2.237199, 1.277159, and 1.005742 folds that of the control, respectively. Conclusions Our results suggest that the low expression of miR‐31 in DMSC s in patients with psoriasis causes an increase in the expression of some of its target genes, which in turn facilitates T lymphocyte activation by inhibiting the proliferation of DMSC s and therefore participates in the pathogenesis of psoriasis.
Combining geometric ray tracing and wave optics propagation, a new simulation model named LWF is established to calculate the full coherent X-ray propagation through a kinoform lens. The LWF model is used to analyze the X-ray propagation through long and short kinoform lenses and calculate the intensity distribution at the focal plane. When the aperture is large, the focal spot for the long kinoform lens is smaller than that for the short kinoform lens. Due to the use of the geometric ray-tracing method to calculate the beam propagation inside the kinoform lens, the LWF model takes a low number of transversal wavefront segments, i.e. a short time, to achieve high accuracy. The simulation times for the one-dimensional and two-dimensional LWF models are 0.025 s and 5.3 s, respectively, with a calculation error of less than 0.5%. The high efficiency and high accuracy make the LWF model a strong tool in designing kinoform lenses.
Psoriasis is a chronic inflammatory skin disease with an unknown pathogenesis. Recently, miR-31 have been shown to play an important role in psoriasis. Moreover, STAT3/p53 pathway has been used in tumor studies, but rarely in psoriasis studies.The present study aimed to investigate the role of STAT3/p53 pathway in psoriasis-like lesions in a mouse model of miR-31 overexpression.All mice (n = 44) were divided into four groups: normal mice treated with Vaseline® (NV; n = 10), normal mice treated with imiquimod (NI; n = 12), miR-31-overexpressing mice treated with Vaseline® (MV; n = 10), and miR-31-overexpressing mice treated with imiquimod (MI; n = 12). Then, we assayed the expression of STAT3 and p53.Our results showed that at the protein level (P < 0.01) and gene level (4.45 times), the expression of STAT3 in the MV group was higher than that in the NV group, and at the protein level (P < 0.01) and gene level (11.43 times), the expression of STAT3 in the MI group was higher than that in the NI group. At the protein level, the expression of p53 in MV group was higher than that in the NV group (P < 0.05), and the expression of p53 in MI group was higher than that in the NI group (P < 0.01).Our findings indicate that overexpression of miR-31 causes upregulation of STAT3, which further brings about upregulation of p53, and eventually leads to serious psoriasis skin lesion.
Abstract Psoriasis is a common chronic inflammatory disease caused by excessive activation of CD4 + T cells, including Th17, Th1, and Th22. The role of CD8 + T cells in psoriasis pathogenesis remains poorly understood. In this study, we aimed to identify the phenotype of CD8 + T cells in patients with psoriasis and to investigate its role in the formation of lesions. First of all, we identify CD8αα + T cell as a main subset of CD8 + T cells infiltrated in lesions of patients with psoriasis. Furthermore, we found that epidermal CD8αα + T cells exhibited tissue-resident memory T cells (T RM ) phenotypes and dermal CD8αα + T cells exhibited effector memory (T EM ) phenotypes in psoriatic lesions. Thereafter, by coculturing CD8αα + T cells with autogenous CD4 + T cells to investigate the function of CD8αα + T cells, we found that CD8αα + T cells from patients with psoriasis could promote the proliferation of CD4 + T effector cells; while CD8αα + T cells from healthy controls exerted immunosuppressive function. Finally, we demonstrate that CD8αα + T cells from patients with psoriasis did not express the markers of regulatory T cells, and produce IL-17 and IFN-γ. In conclusion, our findings demonstrate that CD8αα + T cells contribute to the pathogenesis of psoriasis by producing pro-inflammatory factors.
ErbB3-binding protein 1(Ebp1) has two isoforms, p42 Ebp1 and p48 Ebp1, both of which can regulate cell growth and differentiation. But these isoforms often have opposite effects, including contradictory roles in regulation of cell growth in different tissues and cells. P48 Ebp1 belongs to the full-length sequence, while conformational changes in the crystal structure of p42 Ebp1 reveals a lack of an α helix at the amino terminus. Due to the differences in the structures of these two isoforms, they have different binding partners and protein modifications. Ebp1 can function as both an oncogene and a tumor suppressor factor. However, the underlying mechanisms by which these two isoforms exert opposite functions are still not fully understood. In this review, we summarize the genes and the structures of protein of these two isoforms, protein modifications, binding partners and the association of different isoforms with diseases.
Objective To assess the preferential expressions of peripheral blood T cell receptor beta chain variable region (TRBV) subfamilies in patients with psoriasis vulgaris(PV), and to estimate their role in the pathogenesis of psoriasis. Methods Thirty-three upstream primers were designed to target the human functional TRBV genes, downstream primers to target the common T cell receptor beta constant (TRBC) gene,with T cell receptor alpha constant (TRAC) gene as the internal reference. Total RNA was extracted from the peripheral blood T cells of 10 health human controls and 10 patients with PV, and transcribed into cDNA.Then, TRBV genes were amplified by real-time fluorescence quantitative PCR (RFQ-PCR) and the fluorescence intensity of each samples was detected. The expression levels of TRBV genes in the control group were used to calculate the cut-off values (mean expression levels of TRBV subfamilies in the 10 normal controls + 3 standard deviations). When the expression level of a TRBV subfamily from patients with PV was equal to or higher than the cut-off value, it was considered as the preferentially expressed TRBV subfamily. Results The threshold cycle (Ct) value varied from 21 to 24 for TRAC gene. The difference in the Ct value between TRBV subfamily genes and TRAC gene in patients with PV was 2.98 for TRBV2 gene, 3.24 for TRBV5-7 gene, 2.52 for TRBV6-6/6-9 gene, 2.04 for TRBV 12 gene, 3.56 for TRBV 24 gene, and 4.12 for TRBV 29 gene, and the expression levels of these subfamily genes were significantly higher than those in the normal controls (all P ＜ 0.05). According to the above standard, TRBV6-6/6-9, TRBV12 and TRBV29 were considered to be preferentially expressed subfamilies. Conclusions There is a preferential expression of TRBV gene subfamilies in peripheral blood of patients with psoriasis vulgaris, which may play a vital role in the abnormal T cell-mediated immune responses in psoriasis.
Key words:
Psoriasis; Genes, T cell receptor beta; Complementarity determining region
Abstract Objective Increased angiogenesis is a pathological feature of psoriasis, but the pathomechanisms of angiogenesis in psoriasis are not clear. Interleukin‐17A (IL‐17A) is the major effect factor in the pathogenesis of psoriasis. Our results showed that IL‐17A can promote angiogenesis and cause endothelial cell inflammation. Autophagy plays an important role not only in regulating inflammation, but also in regulating angiogenesis. Whether angiogenesis in psoriasis is related to autophagy remains unclear. In this study, we treated human umbilical vein endothelial cells (HUVECs) with IL‐17A to simulate increased angiogenesis to study whether increased angiogenesis in psoriasis is related to autophagy. Methods and Results Our results showed that treatment of HUVECs with IL‐17A significantly increased angiogenesis and expression levels of mRNA for multiple proinflammatory cytokines (CCL20, IL‐8, CCL2, IL‐6, and IL‐1β) and, while decreasing intracellular levels of nitric oxide (NO) and NO synthase (NOS) activity. Moreover, IL‐17A inhibited autophagy as shown that IL‐17A significantly increased expression levels of LC3II and p62 proteins. Induction of autophagy ameliorated IL‐17A‐mediated inflammatory response and inhibited angiogenesis, accompanied by increased p‐AMPKα(Thr172) and p‐ULK1(Ser555) expression, and decreased p‐mTOR(Ser2448) and p‐ULK1(Ser757) expression. Furthermore, inhibition of either AMPK or lysosomal acidification completely overrode autophagy‐induced changes in angiogenesis and NOS activity. Finally, induction of autophagy decreased apoptosis and caspase‐3 activity in IL‐17A‐treated HUVECs. Conclusions These results showed that IL‐17A is involved in angiogenesis and inflammatory response by inhibiting autophagy through AMPK signaling pathway, suggesting that autophagy may be a new therapeutic target for psoriasis.
Our recent studies found a splice region mutation in C3 accompanied by a significantly increased C3 in psoriatic peripheral blood. Mesenchymal stem cells (MSCs) are a key immunological suppression cell. We further investigate the regulation of MSCs on C3 in psoriasis.We analyzed the C3 and its upstream S100A9, S100A8 and downstream MCP1 in psoriatic and control skin, and in normal human epidermal keratinocytes (NHEKs) co-cultured with psoriatic versus control dermal-derived mesenchymal stem cells (DMSCs) by mRNA, iTRAQ (isobaric tags for relative and absolute quantitative) and simple Western analysis.The mRNA and Simple Western analysis showed that the expression of C3, S100A8 and S100A9 are upregulated in psoriatic lesion (C3: mRNA, 9.23-fold, p = 0.0092; protein, 3.56-fold, p = 0.0244. S100A8: mRNA, 28.35-fold, p = 0.0015; protein, 4.68-fold, p = 0.0215. S100A9: mRNA, 79.45-fold, p = 0.0066; protein, 12.42-fold, p > 0.05). Moreover, the iTRAQ showed that C3 and S100A9 were significantly increased in NHEKs after co-cultured with psoriatic DMSCs compared to that of control DMSCs (C3: 3.40-fold, p = 0, FDR = 0; S100A9: 2.30-fold, p = 9.86E-241, FDR = 6.50E-239), verified by Simple Western. However, the expression of S100A8 and MCP1 was slightly different between the two groups.Our results suggest that psoriatic DMSCs contribute to the increased C3 expression in psoriatic lesion via upregulating S100A9, providing the theoretical basis for the role of C3 and DMSCs in the pathogenesis of psoriasis.
Mesenchymal stem cells (MSCs) have immunoregulatory and proangiogenic effects and are suggested to be involved in the pathological processes of immune-related diseases, including psoriasis. Biological characteristics of bone marrow MSCs (BMSCs) from patients with autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis, but not psoriasis, have been characterized. We compared the gene expression profile and biological characteristics of BMSCs from patients with psoriasis and healthy controls. Although the phenotype, differentiation potential and ability to support CD34(+) cell proliferation were similar to those of normal BMSCs, psoriatic BMSCs showed aberrant proliferative activity, increased apoptosis rate and a characteristic gene expression profile. These aberrations may develop after the abnormal immune response in psoriasis and result in BMSC dysfunction. The functionally deficient BMSCs may then fail to suppress overactive immune cells, thereby contributing to the pathogenesis of psoriasis.
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