Role of the suppressor of cytokine signaling-3 in the pathogenesis of Graves’ orbitopathy

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Март 4, 2025

Objective Graves’ orbitopathy (GO) is characterized by increased production of proinflammatory cytokines and hyaluronic acid fibroblasts their differentiation into adipocytes in response to immunologic stimuli. The suppressor cytokine signaling-3 ( SOCS3 ) an inducible negative regulator the JAK/STAT pathway, implicated various inflammatory diseases. In this study, we investigated role adipogenic pathogenesis GO. Methods Transcriptome profiling orbital tissues obtained from five patients with GO who underwent decompression surgery four healthy subjects was performed using RNA-sequencing. Among top-ranked differentially expressed genes, identified 24 hub genes found be most significantly upregulated gene samples compared that tissue based on quantitative real-time polymerase chain reaction. expression analyzed IL-1β-, IGF-1-stimulated reaction western blot analysis. Knockdown siRNA transfection assess effect phenotype. Results We 184 consistently genes—120 64 downregulated— control. mRNA higher n = 17) control 15). IL-1β IGF-1 enhanced at protein levels. Silencing suppressed levels IL-1β-induced cytokines, including IL-6, IL-8, ICAM-1. Phosphorylation NF-kB Akt attenuated knockdown. Conclusions remarkably adipose induced fibroblasts. inhibition adipogenesis, suggesting may a therapeutic target for controlling mechanisms

Язык: Английский

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Novel inhibitors of STAT3: an updated patent review (2022–present)

Expert Opinion on Therapeutic Patents, Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Signal transducer and activator of transcription 3 (STAT3), a member the STAT protein family, serves as both signal factor. Previous studies have highlighted its pivotal roles in regulating cell proliferation, differentiation, apoptosis, well immune inflammatory responses. Consequently, targeting STAT3 has emerged promising therapeutic strategy for addressing related diseases. This review offers comprehensive summary progress discovering inhibitors, with focus on their structural diversity structure-activity relationships presented patent literature from 2022 to present. Over past decades, significant transformed into target interest drug development. Despite these advances, no STAT3-targeting drugs successfully progressed through late-phase clinical trials, largely due challenges such limited selectivity undesirable side effects. These obstacles highlight inherent complexity developing safe effective inhibitors. Nevertheless, remains highly target, ongoing advancements this field hold potential unlock novel strategies STAT3-related

Язык: Английский

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The Neglected Suppressor of Cytokine Signalling (SOCS): SOCS4-7

Inflammation, Год журнала: 2024, Номер unknown

Опубликована: Окт. 26, 2024

Язык: Английский

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The role of suppressor of cytokine signaling 3 in inflammatory bowel disease and its associated colorectal cancer

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1871(2), С. 167578 - 167578

Опубликована: Ноя. 19, 2024

Язык: Английский

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