rs744166GG in STAT3 and rs7574865TT in STAT4 had higher frequencies in the case than the control group, suggesting these 2 genotypes increase the susceptibility to psoriasis (p < 0.05).
We identified seven susceptibility loci outside the human leukocyte antigen region (9p24 near JAK2, 10q22 at ZMIZ1, 11q13 near PRDX5, 16p13 near SOCS1, 17q21 at STAT3, 19p13 near FUT2, and 22q11 at YDJC) shared between PS and CD with genome-wide significance (p < 5 × 10(-8)) and confirmed four already established PS and CD risk loci (IL23R, IL12B, REL, and TYK2).
Silencing the target gene STAT3 in psoriatic KCs with siRNA combined with ultrasonic irradiation and microbubbles would contribute to a significant innovation as a new clinical therapy for psoriasis.
Taken together, our findings indicated that the curative effects of CTS on psoriasis are accomplished mainly through modulating STAT3, which providing evidences to develop CTS as a potential therapeutic agent for patients with psoriasis.
It has been demonstrated that epidermal Stat3 activation is required for psoriasis development, since keratinocyte-specific Stat3 activation in a mouse model elicits a psoriasis-like phenotype, which is reversed by inhibition of Stat3 signaling.
Using a preclinical model of psoriasis, we show that intradermal injection of APTstat3 tagged with a 9-arginine cell-penetrating peptide (APTstat3-9R) reduced disease progression and modulated psoriasis-related cytokine signaling through inhibition of STAT3 phosphorylation.
Our findings indicate that miR-320b negatively regulates NHEK proliferation by targeting AKT3 to regulate the STAT3 and SAPK/JNK signaling pathways and might participate in the pathogenesis of psoriasis in Chinese Han populations. miR-320b may also be a novel diagnostic marker or therapeutic target for this disease.
Together, our results reveal a novel regulatory mechanism of IL-22 expression by STAT1 through directly antagonizing STAT3, and the importance of the balance between STAT3 and STAT1 in IL-22 regulation and psoriasis pathogenesis.
Our study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23.
Further, AS2762900-00 showed an inhibitory effect on signal transducer and activator of transcription 3 (STAT3) phosphorylation as a downstream signal of IL-23 receptor activation in whole blood from patients with psoriasis.
In conclusion, our results highlight the TRIM27 expression significantly increased by IL-6 and suggest a TRIM27/STAT3-dependent mechanism for regulation of inflammation and proliferation-associated development of psoriasis.
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.