Activation of spleen tyrosine kinase is required for TNF-α-induced endothelin-1 upregulation in human aortic endothelial cells

Yoon Ji Kim; Tai Yeon Koo; Won Seok Yang; Nam Jeong Han; Jin Uk Jeong; Sang Koo Lee; Su-Kil Park

doi:10.1016/j.febslet.2012.01.055

Activation of spleen tyrosine kinase is required for TNF-α-induced endothelin-1 upregulation in human aortic endothelial cells

FEBS Lett. 2012 Mar 23;586(6):818-26. doi: 10.1016/j.febslet.2012.01.055. Epub 2012 Feb 3.

Authors

Yoon Ji Kim¹, Tai Yeon Koo, Won Seok Yang, Nam Jeong Han, Jin Uk Jeong, Sang Koo Lee, Su-Kil Park

Affiliation

¹ Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.

PMID: 22321643
DOI: 10.1016/j.febslet.2012.01.055

Abstract

Endothelin-1 (ET-1) promotes atherosclerosis. We tested whether spleen tyrosine kinase (Syk) mediates tumor necrosis factor-α (TNF-α)-induced ET-1 upregulation in human aortic endothelial cells (HAECs) and sought to identify the signal pathways involved. TNF-α-induced reactive oxygen species (ROS) activated Syk and phosphatidylinositol 3-kinase (PI3K), which was required for the activation of AP-1 and subsequent ET-1 gene transcription. ROS mediated c-Jun NH(2)-terminal kinase (JNK) is also required for AP-1 activation, but Syk and PI3K regulated AP-1 activation independently of JNK. Through regulation of ET-1 production, Syk could be implicated in atherosclerosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aorta / cytology*
Atherosclerosis / physiopathology
Cells, Cultured
Endothelial Cells / cytology
Endothelial Cells / metabolism*
Endothelin-1 / genetics
Endothelin-1 / metabolism*
Enzyme Activation
Enzyme Inhibitors / metabolism
Humans
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
JNK Mitogen-Activated Protein Kinases / metabolism
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / metabolism*
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Reactive Oxygen Species / metabolism
Syk Kinase
Transcription Factor AP-1 / metabolism
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism*
Up-Regulation

Substances

Endothelin-1
Enzyme Inhibitors
Intracellular Signaling Peptides and Proteins
RNA, Small Interfering
Reactive Oxygen Species
Transcription Factor AP-1
Tumor Necrosis Factor-alpha
Phosphatidylinositol 3-Kinases
Protein-Tyrosine Kinases
SYK protein, human
Syk Kinase
JNK Mitogen-Activated Protein Kinases