The main etiopathogenesis of rheumatoid arthritis (RA) is overexpressed inflammatory cytokines and tissue injury mediated by persistent NF-κB activation. MicroRNAs widely participate in the regulation of target gene expression and play important roles in various diseases. Here, we explored the mechanisms of microRNAs in RA. We found that microRNA (miR)-10a was downregulated in the fibroblast-like synoviocytes (FLSs) of RA patients compared with osteoarthritis (OA) controls, and this downregulation could be triggered by TNF-α and IL-1β in an NF-κB-dependent manner through promoting the expression of the YingYang 1 (YY1) transcription factor. Downregulated miR-10a could accelerate IκB degradation and NF-κB activation by targeting IRAK4, TAK1 and BTRC. This miR-10a-mediated NF-κB activation then significantly promoted the production of various inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8, and MCP-1, and matrix metalloproteinase (MMP)-1 and MMP-13. In addition, transfection of a miR-10a inhibitor accelerated the proliferation and migration of FLSs. Collectively, our data demonstrates the existence of a novel NF-κB/YY1/miR-10a/NF-κB regulatory circuit that promotes the excessive secretion of NF-κB-mediated inflammatory cytokines and the proliferation and migration of RA FLSs. Thus, miR-10a acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731824 | PMC |
http://dx.doi.org/10.1038/srep20059 | DOI Listing |
OMICS
January 2025
Biotechnology Institute, Ankara University, Ankara, Turkey.
A systems medicine understanding of the regulatory molecular circuits that underpin breast cancer is essential for early cancer detection and precision/personalized medicine in clinical oncology. Transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) control gene expression and cell biology, and by extension, serve as pillars of the regulatory circuits that determine human health and disease. We report here the development of a regulatory circuit analysis program, , constructing 10 different types of regulatory elements involving messenger RNA, miRNA, lncRNA, and TFs.
View Article and Find Full Text PDFFront Neural Circuits
January 2025
Department of Advanced Medical and Surgical Sciences, Advanced MRI Research Center, University of Campania "Luigi Vanvitelli", Naples, Italy.
The substantia nigra pars compacta (SNc), one of the main dopaminergic nuclei of the brain, exerts a regulatory function on the basal ganglia circuitry via the nigro-striatal pathway but its possible dopaminergic innervation of the thalamus has been only investigated in non-human primates. The impossibility of tract-tracing studies in humans has boosted advanced MRI techniques and multi-shell high-angular resolution diffusion MRI (MS-HARDI) has promised to shed more light on the structural connectivity of subcortical structures. Here, we estimated the possible dopaminergic innervation of the human thalamus via an MS-HARDI tractography of the SNc in healthy human young adults.
View Article and Find Full Text PDFAppl Environ Microbiol
January 2025
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
The biosynthesis of mupirocin, a clinically significant antibiotic produced by sp. NCIMB 10586, is activated by the -acyl homoserine lactone (AHL) MupR/I quorum sensing (QS) system. However, to date, limited research has focused on the influence of global regulators such as the GacS/A two-component system (TCS) on the MupR/I QS system or mupirocin biosynthesis.
View Article and Find Full Text PDFHeliyon
January 2025
Department of Chemical Engineering, Bangladesh University of Engineering and Technology (BUET), Dhaka, 1000, Bangladesh.
The widespread adoption of electronic devices has enhanced living standards but has also led to a surge in electronic waste (e-waste), creating serious environmental and health challenges. Although various methods exist to recover valuable metals from e-waste, each has notable drawbacks. Among these, chemical leaching with aqua regia is widely used but is both highly corrosive and hazardous.
View Article and Find Full Text PDFNature
January 2025
Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood. Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ) is a critical regulator of oral tolerance.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!