IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. 2018 19:1355.įitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, et al. Thymoquinone suppresses IRF-3-mediated expression of type I interferons via suppression of TBK1. A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1. Zhao B, Du F, Xu P, Shu C, Sankaran B, Bell SL, et al. Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation. Ma X, Helgason E, Phung QT, Quan CL, Iyer RS, Lee MW, et al. TBK1 and IKKε act redundantly to mediate STING-induced NF-κB responses in myeloid cells. 2013 587:1230–7.īalka KR, Louis C, Saunders TL, Smith AM, Calleja DJ, D’Silva DB, et al. Recent insights into the complexity of Tank-binding kinase 1 signaling networks: the emerging role of cellular localization in the activation and substrate specificity of TBK1. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Prieto-Alhambra D, Judge A, Javaid MK, Cooper C, Diez-Perez A, Arden NK. Osteoarthritis year in review 2017: clinical. Glyn-Jones S, Palmer AJR, Agricola R, Price AJ, Vincent TL, Weinans H, et al.
Imagej western blot quantification update#
Osteoarthritis: an update with relevance for clinical practice. In conclusion, our results suggest that the TBK1/DRP1 pathway is involved in OA and pharmacological targeting of the TBK1-DRP1 cascade provides prospective therapeutic benefits for the treatment of OA.īijlsma JWJ, Berenbaum F, Lafeber FPJG. In OA mouse models established by surgical destabilization of the medial meniscus, intraarticular injection of lentivirus-TBK1 significantly ameliorated cartilage degradation via regulation of autophagy and alleviation of cell apoptosis. Moreover, we demonstrated that APMK/ULK1 signaling contributed to TBK1 activation. Moreover, TBK1 recruitment and DRP1 phosphorylation at Ser637 was necessary for engulfing damaged mitochondria by autophagosomal membranes during mitophagy. Furthermore, TBK1 overexpression induced remodeling of mitochondrial morphology by directly phosphorylating dynamin-related protein 1 (DRP1) at Ser637, abolishing the fission of DRP1 and preventing its fragmentation function. TBK1 overexpression significantly attenuated TNF-α-induced apoptosis and abnormal mitochondrial function in primary mouse chondrocytes. We demonstrated a strong correlation between TBK1 and OA, evidenced by significantly downregulated expression of TBK1 in cartilage tissue samples of OA patients and in the chondrocytes of aged mice, as well as TNF-α-stimulated phosphorylation of TBK1 in primary mouse chondrocytes. Since a previous study demonstrates a strong correlation between mitophagy and osteoarthritis (OA), we herein investigated the potential role of TBK1 in OA process and mitochondrial functions. Evidence shows that TANK-binding kinase 1 (TBK1) regulates mitochondrial fusion and fission and then mitophagy. Mitochondrial dynamics, including mitochondrial fission and fusion, are critical for maintaining mitochondrial functions.
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