Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches.

作者: Yi-Jen Chen , Wei-An Chang , Ling-Yu Wu , Ching-Fen Huang , Chia-Hsin Chen

DOI: 10.7150/IJMS.35611

关键词: BioinformaticsGeneProto-oncogene tyrosine-protein kinase SrcTranscription factormicroRNABiologyCell adhesionDeep sequencingExtracellular matrix organizationTFAP2A

摘要: Synovitis in osteoarthritis (OA) the consequence of low grade inflammatory process caused by cartilage breakdown products that stimulated production pro-inflammatory mediators fibroblast-like synoviocytes (FLS). FLS participate joint homeostasis and inflammation microenvironment triggers transformation. In current study, we aimed to identify differentially expressed genes potential miRNA regulations human OA through deep sequencing bioinformatics approaches. The 245 were identified, pathway analysis using various databases indicated their enrichment functions related altered extracellular matrix organization, cell adhesion cellular movement. Moreover, among 14 dysregulated with src kinase associated phosphoprotein 2 (SKAP2), adaptor protein complex 1 sigma subunit (AP1S2), PHD finger 21A (PHF21A), lipoma preferred partner (LPP), transcription factor AP-2 alpha (TFAP2A) showed similar expression patterns synovial tissue datasets Gene Expression Omnibus database. Ingenuity Pathway Analysis identified LPP participated migration spreading FLS, which was potentially regulated miR-141-3p. findings suggested new perspectives into understanding novel molecular signatures involved pathogenesis OA, may be therapeutic targets.

参考文章(77)
Roger S. Smith, Eric R. Fedyk, T. A. Springer, N. Mukaida, Barbara H. Iglewski, Richard P. Phipps, IL-8 Production in Human Lung Fibroblasts and Epithelial Cells Activated by the Pseudomonas Autoinducer N-3-Oxododecanoyl Homoserine Lactone Is Transcriptionally Regulated by NF-κB and Activator Protein-2 Journal of Immunology. ,vol. 167, pp. 366- 374 ,(2001) , 10.4049/JIMMUNOL.167.1.366
Marleen MR Petit, Sandra MP Meulemans, Philippe Alen, Torik AY Ayoubi, Erik Jansen, Wim JM Van de Ven, The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus BMC Cell Biology. ,vol. 6, pp. 1- 17 ,(2005) , 10.1186/1471-2121-6-1
S Kuriyama, M Yoshida, S Yano, N Aiba, T Kohno, Y Minamiya, A Goto, M Tanaka, LPP inhibits collective cell migration during lung cancer dissemination Oncogene. ,vol. 35, pp. 952- 964 ,(2016) , 10.1038/ONC.2015.155
Dawid Eckert, Sandra Buhl, Susanne Weber, Richard Jäger, Hubert Schorle, The AP-2 family of transcription factors. Genome Biology. ,vol. 6, pp. 246- 246 ,(2005) , 10.1186/GB-2005-6-13-246
Leilei Zhong, Xiaobin Huang, Marcel Karperien, Janine Post, The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes International Journal of Molecular Sciences. ,vol. 16, pp. 19225- 19247 ,(2015) , 10.3390/IJMS160819225
Noritaka Oyama, Keiji Iwatsuki, Yoshimi Homma, Fumio Kaneko, Induction of transcription factor AP-2 by inflammatory cytokines in human keratinocytes. Journal of Investigative Dermatology. ,vol. 113, pp. 600- 606 ,(1999) , 10.1046/J.1523-1747.1999.00734.X
Patrick H. Finan, Luis F. Buenaver, Sara C. Bounds, Shahid Hussain, Raymond J. Park, Uzma J. Haque, Claudia M. Campbell, Jennifer A. Haythornthwaite, Robert R. Edwards, Michael T. Smith, Discordance between pain and radiographic severity in knee osteoarthritis: Findings from quantitative sensory testing of central sensitization Arthritis & Rheumatism. ,vol. 65, pp. 363- 372 ,(2013) , 10.1002/ART.34646
Marjan M. C. Steenvoorden, Tom W. J. Huizinga, Nicole Verzijl, Ruud A. Bank, H. Karel Ronday, Hilco A. F. Luning, Floris P. J. G. Lafeber, René E. M. Toes, Jeroen DeGroot, Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes. Arthritis & Rheumatism. ,vol. 54, pp. 253- 263 ,(2006) , 10.1002/ART.21523
Manjari Dimri, Jeremy Carroll, Joon Cho, Goberdhan Dimri, microRNA-141 regulates BMI1 expression and induces senescence in human diploid fibroblasts. Cell Cycle. ,vol. 12, pp. 3537- 3546 ,(2013) , 10.4161/CC.26592
Stephanie Lefèvre, Anette Knedla, Christoph Tennie, Andreas Kampmann, Christina Wunrau, Robert Dinser, Adelheid Korb, Eva-Maria Schnäker, Ingo H Tarner, Paul D Robbins, Christopher H Evans, Henning Stürz, Jürgen Steinmeyer, Steffen Gay, Jürgen Schölmerich, Thomas Pap, Ulf Müller-Ladner, Elena Neumann, Synovial fibroblasts spread rheumatoid arthritis to unaffected joints Nature Medicine. ,vol. 15, pp. 1414- 1420 ,(2009) , 10.1038/NM.2050