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Dyrk1A promotes the proliferation, migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis via down-regulating Spry2 and activating the ERK MAPK pathway.
Tissue Cell. 2018 Dec; 55:63-70.TC

Abstract

Fibroblast-like synoviocytes (FLSs) play an essential role in rheumatoid arthritis (RA) by promoting synovitis, pannus growth and cartilage/bone destruction. Increased proliferation, migration and invasion of FLSs greatly contribute to RA initiation and progression. Dual-specificity tyrosine-regulated kinase 1A (Dyrk1A), a serine/threonine kinase, regulates MAPK pathway activation, and governs the proliferation and differentiation of neuronal progenitor cells and cancer cells. Till now, the expression and possible function of Dyrk1A in RA FLSs have not been explored. In this study, we detected an increased expression of Dyrk1A both in the synovial tissues of RA patients and in a TNF-α-induced FLSs activation model. CCK-8 and Edu assays revealed that Dyrk1A knockdown inhibited TNF-α-induced FLSs proliferation. Moreover, inhibiting Dyrk1A expression apparently prevented the migration and invasion capability of FLSs accompanied by a decreased MMP-3 and -9 expression. To investigate the molecular mechanism through which Dyrk1A modulates FLSs activities, we evaluated the effects of Dyrk1A on Spry2, a negativity modulator of ERK MAPK pathway. Western blot assay demonstrated that Dyrk1A silencing significantly increased Spry2 expression and suppressed the phosphorylation of ERK in TNF-α-treated FLSs. Taken together, our results indicated that Dyrk1A might promote FLSs proliferation, migration and invasion by suppressing Spry2 expression and activating the ERK MAPK signaling pathway in RA.

Authors+Show Affiliations

Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Clinical Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China.Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China. Electronic address: zhimingcui@126.com.Department of Orthopedic, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, China. Electronic address: baodianone@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30503061

Citation

Guo, Xiaofeng, et al. "Dyrk1A Promotes the Proliferation, Migration and Invasion of Fibroblast-like Synoviocytes in Rheumatoid Arthritis Via Down-regulating Spry2 and Activating the ERK MAPK Pathway." Tissue & Cell, vol. 55, 2018, pp. 63-70.
Guo X, Zhang D, Zhang X, et al. Dyrk1A promotes the proliferation, migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis via down-regulating Spry2 and activating the ERK MAPK pathway. Tissue Cell. 2018;55:63-70.
Guo, X., Zhang, D., Zhang, X., Jiang, J., Xue, P., Wu, C., Zhang, J., Jin, G., Huang, Z., Yang, J., Zhu, X., Liu, W., Xu, G., Cui, Z., & Bao, G. (2018). Dyrk1A promotes the proliferation, migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis via down-regulating Spry2 and activating the ERK MAPK pathway. Tissue & Cell, 55, 63-70. https://doi.org/10.1016/j.tice.2018.10.002
Guo X, et al. Dyrk1A Promotes the Proliferation, Migration and Invasion of Fibroblast-like Synoviocytes in Rheumatoid Arthritis Via Down-regulating Spry2 and Activating the ERK MAPK Pathway. Tissue Cell. 2018;55:63-70. PubMed PMID: 30503061.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dyrk1A promotes the proliferation, migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis via down-regulating Spry2 and activating the ERK MAPK pathway. AU - Guo,Xiaofeng, AU - Zhang,Dongmei, AU - Zhang,Xing, AU - Jiang,Jiawei, AU - Xue,Pengfei, AU - Wu,Chunshuai, AU - Zhang,Jinlong, AU - Jin,Guohua, AU - Huang,Zhen, AU - Yang,Jian, AU - Zhu,Xinhui, AU - Liu,Wei, AU - Xu,Guanhua, AU - Cui,Zhiming, AU - Bao,Guofeng, Y1 - 2018/10/28/ PY - 2018/08/07/received PY - 2018/10/09/revised PY - 2018/10/20/accepted PY - 2018/12/4/entrez PY - 2018/12/7/pubmed PY - 2019/1/31/medline KW - Dual-specificity tyrosine-regulated kinase1A KW - Fibroblasts-like synocyte KW - Invasion KW - Migration KW - Proliferation KW - Rheumatoid arthritis SP - 63 EP - 70 JF - Tissue & cell JO - Tissue Cell VL - 55 N2 - Fibroblast-like synoviocytes (FLSs) play an essential role in rheumatoid arthritis (RA) by promoting synovitis, pannus growth and cartilage/bone destruction. Increased proliferation, migration and invasion of FLSs greatly contribute to RA initiation and progression. Dual-specificity tyrosine-regulated kinase 1A (Dyrk1A), a serine/threonine kinase, regulates MAPK pathway activation, and governs the proliferation and differentiation of neuronal progenitor cells and cancer cells. Till now, the expression and possible function of Dyrk1A in RA FLSs have not been explored. In this study, we detected an increased expression of Dyrk1A both in the synovial tissues of RA patients and in a TNF-α-induced FLSs activation model. CCK-8 and Edu assays revealed that Dyrk1A knockdown inhibited TNF-α-induced FLSs proliferation. Moreover, inhibiting Dyrk1A expression apparently prevented the migration and invasion capability of FLSs accompanied by a decreased MMP-3 and -9 expression. To investigate the molecular mechanism through which Dyrk1A modulates FLSs activities, we evaluated the effects of Dyrk1A on Spry2, a negativity modulator of ERK MAPK pathway. Western blot assay demonstrated that Dyrk1A silencing significantly increased Spry2 expression and suppressed the phosphorylation of ERK in TNF-α-treated FLSs. Taken together, our results indicated that Dyrk1A might promote FLSs proliferation, migration and invasion by suppressing Spry2 expression and activating the ERK MAPK signaling pathway in RA. SN - 1532-3072 UR - https://www.unboundmedicine.com/medline/citation/30503061/Dyrk1A_promotes_the_proliferation_migration_and_invasion_of_fibroblast_like_synoviocytes_in_rheumatoid_arthritis_via_down_regulating_Spry2_and_activating_the_ERK_MAPK_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0040-8166(18)30296-9 DB - PRIME DP - Unbound Medicine ER -