Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells.
Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling.
['Yang|Bin|B|', 'Li|Wei|W|', 'Zheng|Qichang|Q|', 'Qin|Tao|T|', 'Wang|Kun|K|', 'Li|Jinjin|J|', 'Guo|Bing|B|', 'Yu|Qihong|Q|', 'Wu|Yuzhe|Y|', 'Gao|Yang|Y|', 'Cheng|Xiang|X|', 'Hu|Shaobo|S|', 'Kumar|Stanley Naveen|SN|', 'Liu|Sanguang|S|', 'Song|Zifang|Z|']
D000818:Animals D022782:CCAAT-Enhancer-Binding Protein-beta D002478:Cells, Cultured D054377:Chemokine CXCL12 D004789:Enzyme Activation D051550:I-kappa B Kinase D053582:Interleukin-1alpha D020930:MAP Kinase Kinase Kinases D020935:MAP Kinase Signaling System D008297:Male D009131:Muscle, Smooth, Vascular D032389:Myocytes, Smooth Muscle D051267:NF-E2-Related Factor 2 D012333:RNA, Messenger D034741:RNA, Small Interfering D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D015398:Signal Transduction D015854:Up-Regulation D048051:p38 Mitogen-Activated Protein Kinases
Transforming growth factor β-activated kinase 1 Stromal-derived factor-1 CCAAT-enhancer-binding protein β p38 mitogen-activated protein kinase Nuclear factor erythroid 2-related factor 2 Interleukin-1