Nuclear factor-κB signaling negatively regulates high glucose-induced vascular endothelial cell damage downstream of the extracellular signal-regulated kinase/c-Jun N-terminal kinase pathway

作者：Chen, Yunzhi; Guo, Fang; Ru, Zheng; Kong, Hongru; Sun, Hongwei; Yu, Huajun; Yang, Wenjun; Zhang, Qiyu; Zhou, Mengtao^*

来源：Experimental and Therapeutic Medicine, 2017, 14(4): 3851-3855.

DOI：10.3892/etm.2017.4999

• nuclear factor-kappa B
• high glucose
• vascular endothelial cell
• damage
• extracellular signal-regulated kinase/c-Jun N-terminal kinase

Diabetes mellitus (DM)-induced high blood sugar severely damages vascular endothelial cells (VECs), which are in direct contact with the blood. Diabetic complications cause difficulties in skin wound healing and VECs are important for this process. Previous studies demonstrated that high blood sugar delayed the repair of wounded VECs, but the underlying mechanism has remained elusive. To explore the effects of diabetic conditions on VEC damage, cells were incubated in a medium with high glucose and then subjected to RNA-sequencing based transcriptome analysis. The results revealed that numerous biological processes were altered by HG stress, including extracellular matrix-receptor interaction, NOD-like receptor signaling and the nuclear factor (NF)-kappa B pathway. HG treatment increased the levels of phosphorylated inhibitor of NF-kappa B (I kappa B-alpha), the key NF-kappa B signaling regulator as well as the transcripts of plasminogen activator inhibitor-1 and interleukin-8, two inflammatory response markers. Treatment with extracellular signal-regulated kinase (ERK)- and c-Jun N-terminal kinase (JNK)-specific inhibitors U0126 and sp600125, respectively, led to the activation of I kappa B-alpha; however, the inhibitor of I kappa B-alpha phosphorylation Bay11-7082 did not affect ERK and JNK activity, suggesting that ERK/JNK signaling occurs upstream of NF-kappa B in VECs. The present study provided useful information regarding the effects of diabetes on VECs, which may provide approaches for therapies of diabetes-associated complications in the future.

• 出版日期2017-10
• 单位温州医科大学