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Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype. Global miRNA profiling revealed that miR-143 and miR-145 were differentially upregulated in RA-FLSs compared to OA-FLSs. miR-143 and miR-145 were highly expressed in independent RA-FLSs. The miRNA-target prediction and network model of the predicted targets identified insulinlike growth factor binding protein 5 (IGFBP5) and semaphorin 3A (SEMA3A) as potential target genes downregulated by miR-143 and miR-145, respectively. IGFBP5 level was inversely correlated with miR-143 expression, and its deficiency rendered RA-FLSs more sensitive to TNFα stimulation, promoting IL-6 production and NF-κB activity. Moreover, SEMA3A was a direct target of miR-145, as determined by a luciferase reporter assay, antagonizing VEGF165-induced increases in the survival, migration and invasion of RA-FLSs. Taken together, our data suggest that enhanced expression of miR-143 and miR-145 renders RA-FLSs susceptible to TNFα and VEGF165 stimuli by downregulating IGFBP5 and SEMA3A, respectively, and that these miRNAs could be therapeutic targets.

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기사명 저자명 페이지 원문 목차
dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses Sangho Lim, Jung Ho Sohn, Ja-Hyun Koo, Jung-Won Park, Je-Min Choi pp.1-10

MicroRNA-143 and -145 modulate the phenotype of synovial fibroblasts in rheumatoid arthritis Bong-Ki Hong, Sungyong You, Seung-Ah Yoo, Dohyun Park, Daehee Hwang, Chul-Soo Cho, Wan-Uk Kim pp.1-11

Sex-specific regulation of immune responses by PPARs Hong-Jai Park, Je-Min Choi pp.1-7

Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis Dong Min Lee, In Young Kim, Min Ji Seo, Mi Ri Kwon, Kyeong Sook Choi pp.1-18

The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells Chun-Yu Liu, Tzu-Ting Huang, Pei-Yi Chu, Chun-Teng Huang, Chia-Han Lee, Wan-Lun Wang, Ka-Yi Lau, Wen-Chun Tsai, Tzu-I Chao, Jung-Chen Su, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen pp.1-10

SH3BP4, a novel pigmentation gene, is inversely regulated by miR-125b and MITF Kyu-Han Kim, Tae Ryong Lee, Eun-Gyung Cho pp.1-7

NAMPT enzyme activity regulates catabolic gene expression in gingival fibroblasts during periodontitis Ka Hyon Park, Duck-Kyu Kim, Yun Hyun Huh, Gyuseok Lee, Su-Hyeon Lee, Yunkyung Hong, Sun-Hun Kim, Min-Suk Kook, Jeong-Tae Koh, Jang-Soo Chun, Shee Eun Lee, Je-Hwang Ryu pp.1-10

Serum amyloid A inhibits dendritic cell differentiation by suppressing GM-CSF receptor expression and signaling Ji Cheol Kim, Young Su Jung, Ha Young Lee, Joon Seong Park, Yoe-Sik Bae pp.1-7

Enteric dysbiosis-linked gut barrier disruption triggers early renal injury induced by chronic high salt feeding in mice Jingjuan Hu, Haihua Luo, Jieyan Wang, Wenli Tang, Junqi Lu, Shan Wu, Zhi Xiong, Guizhi Yang, Zhenguo Chen, Tian Lan, Hongwei Zhou, Jing Nie, Yong Jiang, Peng Chen pp.1-12

CCCTC-binding factor is essential to the maintenance and quiescence of hematopoietic stem cells in mice Tae-Gyun Kim, Sueun Kim, Soyeon Jung, Mikyoung Kim, Bobae Yang, Min-Geol Lee, Hyoung-Pyo Kim pp.1-14

참고문헌 (40건) : 자료제공( 네이버학술정보 )

참고문헌 목록에 대한 테이블로 번호, 참고문헌, 국회도서관 소장유무로 구성되어 있습니다.
번호 참고문헌 국회도서관 소장유무
1 Evolving concepts of rheumatoid arthritis 네이버 미소장
2 Firestein GS. Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors?. Arthritis Rheum 1996; 39:1781–1790. 미소장
3 Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. 네이버 미소장
4 The role of microRNA in rheumatoid arthritis and other autoimmune diseases. 네이버 미소장
5 microRNA-126 targeting PIK3R2 promotes rheumatoid arthritis synovial fibro-blasts proliferation and resistance to apoptosis by regulating PI3K/AKT pathway 네이버 미소장
6 MicroRNA-20a negatively regulates expression of NLRP3-inflammasome by targeting TXNIP in adjuvant-induced arthritis fibroblast-like synoviocytes 네이버 미소장
7 Philippe L, Alsaleh G, Pichot A, Ostermann E, Zuber G, Frisch B et al. MiR-20a regulates ASK1 expression and TLR4-dependent cytokine release in rheumatoid fibroblast-like synoviocytes. Ann Rheum Dis 2013; 72:1071–1079. 미소장
8 Yang S, Yang Y. Downregulation of microRNA221 decreases migration and invasion in fibroblastlike synoviocytes in rheumatoid arthritis. Mol Med Rep 2015; 12: 2395–2401. 미소장
9 A comparison of normalization methods for high density oligonucleotide array data based on variance and bias 네이버 미소장
10 Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach 네이버 미소장
11 A Data Integration Methodology for Systems Biology 네이버 미소장
12 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. 네이버 미소장
13 Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV et al. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease. Cell Death Differ 2009; 16: 1590–1598. 미소장
14 Circulating microRNAs as Stable Blood-Based Markers for Cancer Detection 네이버 미소장
15 Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis 네이버 미소장
16 Identification of forensically relevant body fluids using a panel of differentially expressed microRNAs. 네이버 미소장
17 Climent M, Quintavalle M, Miragoli M, Chen J, Condorelli G, Elia L. TGFbeta triggers miR-143/145 transfer from smooth muscle cells to endothelial cells, thereby modulating vessel stabilization. Circ Res 2015; 116: 1753–1764. 미소장
18 Chivukula RR, Shi G, Acharya A, Mills EW, Zeitels LR, Anandam JL et al. An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration. Cell 2014; 157: 1104–1116. 미소장
19 Fibroblast‐like synoviocytes derived from patients with rheumatoid arthritis show the imprint of synovial tissue heterogeneity: Evidence of a link between an increased myofibroblast‐like phenotype and high‐inflammation synovitis 네이버 미소장
20 Binding proteins for the insulin-like growth factors: Structure, regulation and function 네이버 미소장
21 Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-a-induced NF-kB activity by binding to TNFR1 네이버 미소장
22 An essential role of NF-kappaB in the "tumor-like" phenotype of arthritic synoviocytes. 네이버 미소장
23 Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. 네이버 미소장
24 Neuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility: Functional Competition of Collapsin-1 and Vascular Endothelial Growth Factor-165 네이버 미소장
25 Interaction of vascular endothelial growth factor 165 with neuropilin-1 protects rheumatoid synoviocytes from apoptotic death by regulating Bcl-2 expression and Bax translocation. 네이버 미소장
26 Competing autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells. 네이버 미소장
27 Anti-neuropilin-1 peptide inhibition of synoviocyte survival, angiogenesis, and experimental arthritis. 네이버 미소장
28 Experimental validation of miRNA targets 네이버 미소장
29 Experimental strategies for microRNA target identification 네이버 미소장
30 Applications of systems approaches in the study of rheumatic diseases 소장
31 Identification of non-coding RNAs embracingcluster 네이버 미소장
32 Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. 네이버 미소장
33 Characterization of global microRNA expression reveals oncogenic potential of miR-145 in metastatic colorectal cancer 네이버 미소장
34 Analysis of the combined action of miR-143 and miR-145 on oncogenic pathways in colorectal cancer cells reveals a coordinate program of gene repression. 네이버 미소장
35 miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. 네이버 미소장
36 Decreased Semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis 네이버 미소장
37 Kolodkin AL, Matthes DJ, Goodman CS. The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 1993; 75: 1389–1399. 미소장
38 Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor. 네이버 미소장
39 Vascular endothelial growth factor levels in the serum and synovial fluid of patients with rheumatoid arthritis 네이버 미소장
40 Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. 네이버 미소장

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