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Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis

ABSTRACT: Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis

PROVIDER: PRJNA1252014 | ENA |

REPOSITORIES: ENA

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Near-infrared light-driven metabolic reprogramming of synoviocytes for the treatment of rheumatoid arthritis

Project description:Rheumatoid arthritis is a common autoimmune disease characterized by chronic synovial inflammation and joint destruction, primarily driven by imbalance cellular metabolism and inflammatory microenvironment. While gene therapy offers a promising therapeutic approach, its effectiveness is limited by the challenges of non-specific gene expression in healthy tissues. In the present study, we developed a gene delivery system (namely APPC), in which near-infrared (NIR)-responsive gold nanorods (AR) were coated with chondroitin sulfate-modified polyethyleneimine (CS-PEI) to facilitate the heat-responsive targeted delivery of heme oxygenase 1 (HO-1) gene. The APPC showed favorable transfection efficiency due to its targeting ability and significantly facilitate the HO-1 expression under NIR irradiation. The combination of APPC/pHO-1 and NIR could effectively reprogram the cellular metabolism and repolarize the macrophages and fibroblast-like synoviocytes (FLSs), thereby inhibiting the inflammation by suppressing the glycolysis. Meanwhile, APPC could specifically enhance the HO-1 expression in inflamed tissues through NIR-mediated the activation of HSP70 promoter, ensuring the precise gene expression via photothermal conversion. In a collagen-induced arthritis (CIA) model, APPC/pHO-1 under NIR irradiation exhibited potent therapeutic efficacy, restoring the articular microenvironmental homeostasis and mitigating the symptoms of RA. These findings highlighted the potential of APPC/pHO-1 nanoparticles in the gene therapy of RA and other inflammatory diseases.

2025-04-17 | GSE294905 | GEO

lncRNA and mRNA expression profiles in fibroblast-like synoviocytes from rheumatoid arthritis patients and trauma patients

Project description:Fibroblast-like synoviocytes (FLSs) are critical for synovial aggressiveness and joint destruction in rheumatoid arthritis (RA).The role and expression patterns of long noncoding RNAs (lncRNAs) in RA are largely unknown. We performed lncRNA and mRNA microarrays to identify differentially expressed lncRNAs and mRNAs in fibroblast-like synoviocytes from rheumatoid arthritis patients compared with fibroblast-like synoviocytes from trauma patients.

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RNA expression profiles in fibroblast-like synoviocytes from rheumatoid arthritis patients and trauma patients

Project description:LncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in fibroblast-like synoviocytes from rheumatoid arthritis patients compared with fibroblast-like synoviocytes from trauma patients. Fibroblast-like synoviocytes were isolated from synovial tissues. LncRNA and mRNA microarrays were performed using fibroblast-like synoviocytes at passage 3.

2016-06-10 | E-GEOD-83147 | biostudies-arrayexpress

RNA expression profiles in fibroblast-like synoviocytes from rheumatoid arthritis patients and trauma patients

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ATF6αis required for the inflammation and survival in rheumatoid arthritis fibroblast-like synoviocytes

Project description:To characterize transcriptome changes upon ATF6α knockdown by the siRNA in rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs)

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Transcriptional responses to TNF following HFl treatment of primary rheumatoid arthritis fibroblast like synoviocytes (RA-FLS)

Project description:We report the effects of Hfol on TNF induction of inflammatory genes in wild type cells versus cells depleted of GCN2 RNA-seq analysis of primary rheumatoid arthritis fibroblast like synoviocytes (RA-FLS) treated with TNFa in the presence or absence of Halofuginone (HF).

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Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes

Project description:Comprehensive Epigenetic Landscape of Rheumatoid Arthritis Fibroblast-like Synoviocytes

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Role of mTOR signaling in mesenchamyl tissue response to inflammation in rheumatoid arthritis

Project description:To investigate the impact of mTOR inhibiton on TNFalpha-activated rheumatoid arthritis fibbroblast-like synoviocytes (RA-FLS)

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Effects of methotrexate and tofacitinib on gene expression of activated rheumatoid arthritis fibroblast-like synoviocytes

Project description:Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.

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Identification of genes regulating TRAIL-induced apoptosis in rheumatoid arthritis fibroblasts-like synoviocytes (RA FLS)

Project description:Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease involving primarily the synovial membranes and articular structures of multiple joints. A hallmark of RA is the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLS), as these cells invade and finally destroy the joint structure. RA FLS have been therefore proposed as a therapeutic target. > TNF-related apoptosis-inducing ligand (TRAIL) has been described as a pro-apoptotic factor on malignant cells. The fact that fibroblasts-like-synoviocytes (FLS) in rheumatoid arthritis RA patients exhibit tumor like features led us to investigate the effect of TRAIL on ex-vivo RA FLS. We have previously described that TRAIL induces apoptosis only in a subset of RA FLS, but an induction of proliferation in the surviving cells. This observation corresponds to the pleiotropic effects of TRAIL observed on primary human tumor cells. We also observed that sensitivity to TRAIL-induced apoptosis varied in RA FLS from one patient to another, and was correlated with disease severity. We therefore screened for genes that were differentially expressed in RA FLS sensitive and resistant to TRAIL induced apoptosis in order to understand molecular factors making cells resistant or sensitive to TRAIL induced apoptosis.

2018-02-12 | GSE65908 | GEO

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