Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR-1 and -2 and VEGFR2 in endothelial cells.
Angiogenesis and inflammation are regarded as important factors in the pathogenesis of chronic inflammation, cancer, and wound healing. Recent studies have supported prior evidence that common signaling pathways are involved in angiogenesis and inflammatory responses; however, key factors controlling both processes remain unclear. Although tripartite motif-containing (TRIM)-28 is known to have an immunosuppressive role in immune cells, its expression level and role in endothelial cells (ECs) are still unclear. In this study, we investigated the role of TRIM28 in inflammatory responses and angiogenic activity of ECs for the first time. We showed that TRIM28 is the most abundant TRIM family member and is localized in nuclei of ECs. Small interfering RNA-mediated knockdown of TRIM28 strikingly suppressed expression of TNF receptor (TNFR)-1 and -2, decreased TNF-α-induced phosphorylation of IKKα/β and IκBα and degradation of IκBα and nuclear translocation of p65, and suppressed basal level and TNF-α-induced expression of chemokines and adhesion molecules, including VCAM-1, IL-6, ICAM-1, E-selectin, and monocyte chemoattractant protein (MCP)-1. Unexpectedly, IL-8 was potentiated by TRIM28 knockdown in ECs in an NF-κB-inducing kinase-dependent manner. Meanwhile, knockdown of TRIM28 inhibited expression of VEGF receptor 2 and suppressed VEGF-induced proliferation and tube formation by ECs. Finally, knockdown of TRIM28 suppressed recruitment of ECsin vivoin a murine synthetic basement membrane model. In summary, we found that TRIM28 acts as a central factor in controlling endothelial inflammatory responses and angiogenic activities by retaining expression of TNFR-1 and -2 and VEGF receptor 2 in ECs.-Wang, Y., Li, J., Huang Y., Dai, X., Liu, Y., Liu, Z., Wang, Y., Wang, N., Zhang, P. Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR1 and -2 and VEGFR2 in endothelial cells.
Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yinfang
Y
Wang
Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Jinping
J
Li
Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yitong
Y
Huang
Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Xiuqin
X
Dai
Department of Cardiovascular Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Youbin
Y
Liu
Department of Cardiovascular Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Zongjun
Z
Liu
Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, Florida, USA; and.
Ying
Y
Wang
The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.
Nanping
N
Wang
Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; zhangnep@hotmail.com.|Department of Cardiovascular Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Peng
P
Zhang
D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000076183:Tripartite Motif-Containing Protein 28; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
D016209:Interleukin-8; D017346:Protein Serine-Threonine Kinases; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012097:Repressor Proteins; D000076183:Tripartite Motif-Containing Protein 28; D014409:Tumor Necrosis Factor-alpha; D040301:Vascular Endothelial Growth Factor Receptor-2; D000097782:NF-kappaB-Inducing Kinase; C508606:CXCL8 protein, human; C101116:TRIM28 protein, human; C000588866:KDR protein, human
KMT5B; NF-κB; TRIM28