Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells - PubMed (original) (raw)
. 2001 Jan;15(1):230-242.
doi: 10.1096/fj.00-0247com.
Affiliations
- PMID: 11149911
- DOI: 10.1096/fj.00-0247com
Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells
D Mechtcheriakova et al. FASEB J. 2001 Jan.
Abstract
Tissue factor (TF) has been shown to be up-regulated in endothelial cells by the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) as well as by the main angiogenic factor VEGF. Since both stimuli induce the transcription factor EGR-1, which is critically involved in TF gene regulation, we used EGR-1-dependent TF induction as a model to identify potential cross-talks between the various signal transduction cascades initiated by VEGF and TNF-alpha. The data show that at the MAP kinase level, VEGF mainly activates ERK1/2 and p38 MAP kinases in human endothelial cells. TNF-alpha is able to activate all three MAP kinase cascades as well as the classical inflammatory IkappaB/NFkappaB pathway. Furthermore, the MEK/ERK module of MAP kinases appears to act as the convergence point of VEGF- and TNF-alpha-initiated signaling cascades, which lead to the activation of EGR-1 and subsequent TF expression, whereas the upstream signals are distinct. We found that induction of TF by VEGF via EGR-1 is strongly PKC dependent. The TNF-alpha-initiated MEK/ERK cascade connected to EGR-1 and TF expression is clearly less sensitive to PKC inhibition. TNF-alpha-mediated activation of MEK/ERK and EGR-1 can be blocked by adenoviral expression of a dominant negative mutant of IKK2, whereas the VEGF signaling pathway is unaffected. Thus, our data demonstrate a new link between the classical inflammatory IKK/IkappaB and the MEK/ERK cascades triggered by TNF-alpha. The additional finding that EGF induces ERK and EGR-1 in a PKC-independent manner and that this signal is not sufficient to up-regulate TF emphasizes the importance of a VEGF-specific signaling pattern for the induction of TF.
Similar articles
- Vascular endothelial growth factor KDR receptor signaling potentiates tumor necrosis factor-induced tissue factor expression in endothelial cells.
Shen BQ, Lee DY, Cortopassi KM, Damico LA, Zioncheck TF. Shen BQ, et al. J Biol Chem. 2001 Feb 16;276(7):5281-6. doi: 10.1074/jbc.M007969200. Epub 2000 Oct 31. J Biol Chem. 2001. PMID: 11058594 - Functional role of Egr-1 mediating VEGF-induced tissue factor expression in the retinal capillary endothelium.
Sassa Y, Hata Y, Murata T, Yamanaka I, Honda M, Hisatomi T, Fujisawa K, Sakamoto T, Kubota T, Nakagawa K, Sueishi K, Ishibashi T. Sassa Y, et al. Graefes Arch Clin Exp Ophthalmol. 2002 Dec;240(12):1003-10. doi: 10.1007/s00417-002-0576-6. Epub 2002 Nov 6. Graefes Arch Clin Exp Ophthalmol. 2002. PMID: 12483323 - Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family.
Zachary I, Gliki G. Zachary I, et al. Cardiovasc Res. 2001 Feb 16;49(3):568-81. doi: 10.1016/s0008-6363(00)00268-6. Cardiovasc Res. 2001. PMID: 11166270 Review. - Signals and genes induced by angiogenic growth factors in comparison to inflammatory cytokines in endothelial cells.
Schweighofer B, Schultes J, Pomyje J, Hofer E. Schweighofer B, et al. Clin Hemorheol Microcirc. 2007;37(1-2):57-62. Clin Hemorheol Microcirc. 2007. PMID: 17641395 Free PMC article. Review.
Cited by
- Singularity and Commonality in Response to SARS-CoV-2 in Lung and Colon Cell Models.
Meshcheryakova A, Zimmermann P, Salzmann M, Pietschmann P, Mechtcheriakova D. Meshcheryakova A, et al. Int J Mol Sci. 2022 Sep 9;23(18):10451. doi: 10.3390/ijms231810451. Int J Mol Sci. 2022. PMID: 36142362 Free PMC article. - EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death.
Lehman CW, Smith A, Kelly J, Jacobs JL, Dinman JD, Kehn-Hall K. Lehman CW, et al. Viruses. 2022 Jun 2;14(6):1210. doi: 10.3390/v14061210. Viruses. 2022. PMID: 35746681 Free PMC article. - Dichotomous Role of Tumor Necrosis Factor in Pulmonary Barrier Function and Alveolar Fluid Clearance.
Lucas R, Hadizamani Y, Enkhbaatar P, Csanyi G, Caldwell RW, Hundsberger H, Sridhar S, Lever AA, Hudel M, Ash D, Ushio-Fukai M, Fukai T, Chakraborty T, Verin A, Eaton DC, Romero M, Hamacher J. Lucas R, et al. Front Physiol. 2022 Feb 21;12:793251. doi: 10.3389/fphys.2021.793251. eCollection 2021. Front Physiol. 2022. PMID: 35264975 Free PMC article. Review. - The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy.
Khezri MR, Varzandeh R, Ghasemnejad-Berenji M. Khezri MR, et al. Cell Mol Biol Lett. 2022 Jan 11;27(1):6. doi: 10.1186/s11658-022-00308-w. Cell Mol Biol Lett. 2022. PMID: 35016612 Free PMC article. Review. - GPR43 activation-mediated lipotoxicity contributes to podocyte injury in diabetic nephropathy by modulating the ERK/EGR1 pathway.
Lu J, Chen PP, Zhang JX, Li XQ, Wang GH, Yuan BY, Huang SJ, Liu XQ, Jiang TT, Wang MY, Liu WT, Ruan XZ, Liu BC, Ma KL. Lu J, et al. Int J Biol Sci. 2022 Jan 1;18(1):96-111. doi: 10.7150/ijbs.64665. eCollection 2022. Int J Biol Sci. 2022. PMID: 34975320 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous