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Biological regulation on synovial fibroblast and the treatment of rheumatoid arthritis by nobiletin-loaded tetrahedral framework nucleic acids cargo tank

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Chinese Chemical Letters 2023年第2期34卷 446-451页

作者： Yuting Wen Mei Zhang Yangxue Yao Yang Gao Xiaolin Zhang Yunfeng Lin Xiaoxiao Cai State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

The hyperplasia and destruction of synovial tissue have an important impact on the development of rheumatoid arthritis(RA), the abnormal proliferation and migration of synovial fibroblast in synovial tissue is similar to tumor cells. Targeting anomalous synovial fibroblast and designing a high bioavailability nano drug delivery system can reduce the dosage for the treatment of rheumatoid arthritis and it is of great significance to reduce toxic and side effects and improve curative effect. In this experiment, the nobiletin-loaded tetrahedral framework nucleic acids cargo tank was established, carrying antiinflammatory small molecule monomer drug nobiletin with minimal bioavailability. Both in vitro cell experiments and in vivo animal studies proved the nano cargo tank enhance the role of nobiletin in reducing the invasiveness of pathological synovial fibroblast and promote their apoptosis, effectively alleviate the disease development of rheumatoid arthritis.

关键词： Tetrahedral framework nucleic acids Nobiletin Rheumatoid arthritis synovial fibroblast Apoptosis

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TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling

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Cellular & Molecular Immunology 2018年第7期15卷 685-696页

作者： Lin Wang Hongyan Dong Guanhua Song Rui Zhang Jihong Pan Jinxiang Han Department of Biochemistry and Molecular Biology Shandong University School of MedicineJinanShandongChina Research Center for Medicinal Biotechnology Key Laboratory for Rare and Uncommon Diseases of Shandong ProvinceShandong Academy of Medical SciencesJinanShandongChina Department of Pathology Linyi People's HospitalLinyiChina Institute of Basic Medicine Shandong Academy of Medical SciencesJinanShandongChina

The upregulated expression of thioredoxin domain-containing protein 5(TXNDC5)is associated with rheumatoid arthritis in patients and model ***,the underlying mechanism by which TXNDC5 influences the pathological activation of rheumatoid arthritis synovial fibroblasts(RASFs)remains *** this study,we show that TXNDC5 expression in RASFs and their cytokine production are significantly upregulated in response to LPS,TNF-αand IL-6,but suppressed by transfection with ***5 is further validated as the direct target of NF-κB ***,TXNDC5 directly interacts with heat shock cognate 70 protein(HSC70)to sequester it in the cytoplasm,and HSC70 silencing exerts the same effects as TXNDC5 on the biological activity of RASFs(for example,decreased cell viability,invasion and cytokine production).Furthermore,HSC70 activates NF-κB signaling by destabilizing IκBβprotein in the absence of LPS or facilitating its nuclear translocation in the presence of ***,TXNDC5 can also regulate the activity of NF-κB signaling in a HSC70-IκBβ-dependent *** together,by linking HSC70 and NF-κB signaling,TXNDC5 plays a pro-inflammatory role in RASFs,highlighting a potential approach to treat RA by blocking the TXNDC5/HSC70 interaction.

关键词： cytokine inflammation rheumatoid arthritis synovial fibroblast TXNDC5

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