title: CD137 Regulates NFATc1 Expression in Mouse VSMCs through TRAF6/NF-κB p65 Signaling Pathway.
abstract: Our previous study proved that CD137-CD137L interaction can regulate the expression of NFATc1. Here, we investigated whether CD137 signaling regulates the expression of NFATc1 in mice VSMCs through TRAF6/NF-κB p65 pathway. Data shows that the CD137 expression can be stimulated by TNF-α in a time-dependent manner in mouse VSMCs. Knockdown of TRAF6 by siTRAF6 significantly attenuated agonist-CD137mAb induced increase of NF-κB p65 and NFATc1 in VSMCs. Pretreatment with a NF-κB inhibitor PDTC for 30 min inhibited the expression of p-p65 in both cytoplasm and nucleus in VSMCs. Thus, the protein level of NFATc1 can be suppressed through inhibition of p-p65. Finally, we also show that the levels of IL-2 and IL-6 can be increased by agonist-CD137 stimulation and decreased when NFATc1 was suppressed. Our data suggest that activated CD137 signaling regulates the expression of NFATc1 and its downstream factors through TRAF6/NF-κB p65 pathways in VSMCs. These findings provide a novel target for treatment of atherosclerosis.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.
authors.forename: Zhongqun
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology*; D032389:Myocytes, Smooth Muscle / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D048029:TNF Receptor-Associated Factor 6 / Q000502:physiology*; D051996:Transcription Factor RelA / Q000502:physiology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000032:analysis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D048029:TNF Receptor-Associated Factor 6; D051996:Transcription Factor RelA; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha