It was observed that 'psoriasis 1' downregulated the concentrations of TNF‑α, IFN‑γ, IL‑22, IL‑17C, IL‑1β and IL‑4, and upregulated the concentration of 25HVD3; furthermore, 'psoriasis 1' downregulated the expression levels of NF‑κB, phosphorylated (p)‑NF‑κB, IKK, p‑IKK, STAT3, p‑STAT3, STAT4 and p‑STAT4, and upregulated the expression level of VDR in TNF‑α‑induced HaCaT cells.
STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, and a similar upregulation was seen in skin biopsies from EN [84.7 vs 22.3, p < 0.001] and PG [60.5 vs 22.3, p = 0.011], but not in psoriasis.
Several mouse models of psoriasis including drug-induced models (topical application of imiquimod to the skin) and genetically engineered mice (constitutive activation of epidermal STAT3, epidermal deletion of JunB/c-Jun, and epidermal overexpression of Tie2) have been used to study the pathophysiology of the disease; however such models cannot fully recapitulate all molecular and cellular pathways occurring in human psoriasis.
We also found that IL-22 increases CD147 transcription in vitro and in vivo and that Stat3 binds directly to the CD147 promoter between positions -854 and -440, suggesting that CD147 expression is up-regulated in patients with psoriasis through Stat3 activation.
We further show that overexpression of hsa-miR-4516 downregulates STAT3, p-STAT3, CDK6, and UBE2N proteins that are consistently upregulated in psoriasis and induces apoptosis in HaCaT cells.
All psoriasis lesions also had detectable levels of activated Stat3, a protein indicated in development of the disease, whereas control tissue lacked this protein.
Herein, we reported that K17 could be modified through ubiquitination that controlled its stability and led to the phosphorylation and nuclear translocation of its interactor signal transducers and activators of transcription 3 (STAT3), which is a key regulator of cell proliferation in psoriasis.
Several common TFs that bind the promoters of the DEGs, including the well-known signal transducer and activator of transcription 1 (STAT1), STAT3, and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) as well as ETS homologous factor (EHF), Fos-like antigen 1 (FOSL1), and Forkhead box C1 (FOXC1), which are rarely studied in psoriasis, were also identified.
To examine the role of Notch-1 signalling in the pathogenesis of psoriasis, Notch-1, DLL-4, Jagged-1, Hrt-1/Hrt-2, A-SAA, Factor VIII and vascular endothelial growth factor (VEGF) mRNA and/or protein expression in psoriasis skin biopsies, serum and dHMVEC were assessed by immunohistology, dual-immunofluorescence, real-time PCR, ELISA and Western blotting.
Although increased expression of vascular endothelial growth factor protein was detected in the epidermis, the intensity of this staining was weak compared with the epidermal staining in psoriatic lesions and compared with the strong vascular endothelial growth factor mRNA signal in chronic wounds and psoriasis.
Potential value as a novel marker of angiogenesis in patients with psoriasis is also evaluated by assessing possible relation of SCUBE-1 and 3 with disease activity in conjunction with vascular endothelial growth factor (VEGF) levels, as an established marker of angiogenesis.
Also, up-regulation of psoriasis-associated cytokine profiles, including VEGF, was inhibited in the skin from K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice following 4OHT treatment.
In addition, VPF/VEGF is strongly expressed by epidermal keratinocytes in wound healing and psoriasis, disorders that are also characterized by increased microvascular permeability and angiogenesis.
Topical application or subcutaneous injection of the Fib3 antibody decreased Psoriasis Area and Severity Index and VEGF expression in imiquimod-treated mice.
Psoriasis (Ps) is an autoimmune disease characterized by keratinocyte hyperproliferation and chronic inflammation, with increased expression of tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF).
Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis.
However, there was no significant difference in IL-13 gene expression in the skin of patients with psoriasis (n = 10) and that of healthy control subjects.
Moreover, a significant negative correlation was found between TNFAIP3 mRNA in psoriatic tissue and psoriasis area severity index values (rs = -0.382, P-value = 0.037).