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http://dx.doi.org/10.4062/biomolther.2015.088

Aspirin-Triggered Resolvin D1 Inhibits TGF-β1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress  

Shu, Yusheng (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital)
Liu, Yu (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital)
Li, Xinxin (Department of Cardiothoracic Surgery, Subei People's Hospital)
Cao, Ling (Department of Endocrinology, Clinical Medicine College of Yangzhou University, Subei People's Hospital)
Yuan, Xiaolong (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital)
Li, Wenhui (Department of Cardiothoracic Surgery, Clinical Medicine College of Yangzhou University, Subei People's Hospital)
Cao, Qianqian (Department of Cardiothoracic Surgery, Subei People's Hospital)
Publication Information
Biomolecules & Therapeutics / v.24, no.2, 2016 , pp. 132-139 More about this Journal
Abstract
The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmed that occur in various pathologic conditions. Transforming growth factor ${\beta}1$ (TGF-${\beta}1$) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (AT-RvD1) has been known to be involved in the resolution of inflammation, but whether it has effects on TGF-${\beta}1$-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-${\beta}1$ reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE-cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory ${\kappa}B$ kinase 16 (IKK 16), which is known to inhibit the NF-${\kappa}B$ pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-${\beta}1$-induced EndMT, but it had no effect on TGF-${\beta}1$-induced EndMT alone. Smad7, which is a key regulator of TGF-${\beta}$/Smads signaling by negative feedback loops, was significantly increased with the treatment of AT-RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-${\beta}1$-induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress.
Keywords
TGF-${\beta}1$-induced endothelial-mesenchymal transition; Aspirin-triggered resolvin D1; Human umbilical vein vascular endothelial cells line (HUVECs); Inhibitor of $I{\kappa}B$ kinase; Smad7;
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1 Zhang, X., Wang, T., Gui, P., Yao, C., Sun, W., Wang, L., Wang, H., Xie, W., Yao, S., Lin, Y. and Wu, Q. (2013) Resolvin D1 reverts lipopolysaccharide-induced TJ proteins disruption and the increase of cellular permeability by regulating $I{\kappa}B{\alpha}$ signaling in human vascular endothelial cells. Oxid. Med. Cell. Longev. 2013, 185715.
2 Allen, M. and Louise Jones, J. (2011) Jekyll and Hyde: the role of the microenvironment on the progression of cancer. J. Pathol. 223, 162-176.
3 Aisagbonhi, O., Rai, M., Ryzhov, S., Atria, N., Feoktistov, I. and Hatzopoulos, A. K. (2011) Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition. Dis. Model. Mech. 4, 469-483.   DOI
4 Anastasiou, D., Poulogiannis, G., Asara, J. M., Boxer, M. B., Jiang, J. K., Shen, M., Bellinger, G., Sasaki, A, T., Locasale, J, W., Auld, D,S., Thomas, C,J., Heiden, M, G, V. and Cantley, L. C. (2011) Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334, 1278-1283.   DOI
5 Benton, R. L., Maddie, M. A., Dincman, T. A., Hagg, T. and Whittemore, S. R. (2009) Transcriptional activation of endothelial cells by $TGF{\beta}$ coincides with acute microvascular plasticity following focal spinal cord ischaemia/reperfusion injury. ASN Neuro. 1, 181-184.   DOI
6 Churchman, A. T., Anwar, A. A., Li, F. Y., Sato, H., Ishii, T., Mann, G. E. and Siow, R. (2009) Transforming growth factor-$\beta$1 elicits Nrf2-mediated antioxidant responses in aortic smooth muscle cells. J. Cell. Mol. Med. 13, 2282-2292.   DOI
7 Cox, Jr, R., Phillips, O., Fukumoto, J., Fukumoto, I., Tamarapu Parthasarathy, P., Arias, S., Cho, Y., Lockey, R. F. and Kolliputi, N. (2015) Aspirin-Triggered Resolvin D1 Treatment Enhances Resolution of Hyperoxic Acute Lung Injury. Am. J. Respir. Cell Mol. Biol. 53, 422-435.   DOI
8 Choi, H. Y., Lee, H. G., Kim, B. S., Ahn, S. H., Jung, A., Lee, M., Lee, J.E., Kim, H. J., Ha, S. K. and Park, H. C. (2015) Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction. Stem Cell Res. Ther. 6, 18.   DOI
9 Edens, H. A. and Parkos, C. A. (2000) Modulation of epithelial and endothelial paracellular permeability by leukocytes. Adv. Drug Deliv. Rev. 41, 315-328.   DOI
10 Emmanuel, C., Huynh, M., Matthews, J., Kelly, E. and Zoellner, H. (2013) TNF-${\alpha}$ and TGF-$\beta$ synergistically stimulate elongation of human endothelial cells without transdifferentiation to smooth muscle cell phenotype. Cytokine 61, 38-40.   DOI
11 Garside, V. C., Chang, A. C., Karsan, A. and Hoodless, P. A. (2013) Co-ordinating Notch, BMP, and TGF-$\beta$ signaling during heart valve development. Cell. Mol. Life Sci. 70, 2899-2917.   DOI
12 Gonzalez, D. M. and Medici, D. (2014) Signaling mechanisms of the epithelial-mesenchymal transition. Sci. Signal. 7, re8.   DOI
13 Jaffe, E. A., Nachman, R. L., Becker, C. G. and Minick, C. R. (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J. Clin. Invest. 52, 2745-2756.   DOI
14 Goumans, M. J., Valdimarsdottir, G., Itoh, S., Lebrin, F., Larsson, J., Mummery, C., Karlsson, S. and ten Dijke, P. (2003) Activin receptor-like kinase (ALK) 1 is an antagonistic mediator of lateral $TGF{\beta}$/ ALK5 signaling. Mol. Cell 12, 817-828.   DOI
15 Harrison, J. L., Rowe, R. K., Ellis, T. W., Yee, N. S., O'Hara, B. F., Adelson, P. D. and Lifshitz, J. (2015) Resolvins AT-D1 and E1 differentially impact functional outcome, post-traumatic sleep, and microglial activation following diffuse brain injury in the mouse. Brain Behav. Immun. 47, 131-140.   DOI
16 Inoue, Y. and Imamura, T. (2008) Regulation of TGF-$\beta$ family signaling by E3 ubiquitin ligases. Cancer Sci. 99, 2107-2112.   DOI
17 Krizbai, I. A., Gasparics, A., Nagyoszi, P., Fazakas, C., Molnar, J., Wilhelm, I., Bencs R,. Rosivall L. and Sebe, A. (2015) Endothelial-Mesenchymal Transition of Brain Endothelial Cells: Possible Role during Metastatic Extravasation. PLoS One 10, e0119655.   DOI
18 Kevil, C. G., Oshima, T., Alexander, B., Coe, L. L. and Alexander, J. S. (2000) $H_2O_2$-mediated permeability: role of MAPK and occludin. Am. J. Physiol. Cell Physiol. 279, C21-C30.   DOI
19 Kobayashi, M. and Yamamoto, M. (2005) Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid. Redox Signal. 7, 385-394.   DOI
20 Kashihara, N., Haruna, Y., Kondeti, V. K. and Kanwar, Y. S. (2010) Oxidative stress in diabetic nephropathy. Curr. Med. Chem. 17, 4256-4269.   DOI
21 Ng, Y. Y., Hou, C. C., Wang, W., Huang, X. R. and Lan, H. Y. (2005) Blockade of $NF{\kappa}B$ activation and renal inflammation by ultrasoundmediated gene transfer of Smad7 in rat remnant kidney. Kidney Int. Suppl. 67, S83-S91.   DOI
22 Kaneda, H., Arao, T., Matsumoto, K., De Velasco, M. A., Tamura, D., Aomatsu, K., Kudo, K., Sakai, K., Nagai, T., Fujita, Y., Tanaka, K., Yanagihara, K., Yamada, Y., Okamato, I., Nakagawa, K. and Nishio, K. (2011) Activin A inhibits vascular endothelial cell growth and suppresses tumour angiogenesis in gastric cancer. Br. J. Cancer 105, 1210-1217.   DOI
23 Lee, H. J., Park, M. K., Lee, E. J. and Lee, C. H. (2013) Resolvin D1 inhibits TGF-$\beta{1}$-induced epithelial mesenchymal transition of A549 lung cancer cells via lipoxin A4 receptor/formyl peptide receptor 2 and GPR32. Int. J. Biochem. Cell Biol. 45, 2801-2807.   DOI
24 Medici, D., Shore, E. M., Lounev, V. Y., Kaplan, F. S., Kalluri, R. and Olsen, B. R. (2010) Conversion of vascular endothelial cells into multipotent stem-like cells. Nat. Med. 16, 1400-1406.   DOI
25 Ryoo, I. G., Ha, H. and Kwak, M. K. (2014) Inhibitory role of the KEAP1- NRF2 pathway in $TGF{\beta}1$-stimulated renal epithelial transition to fibroblastic cells: a modulatory effect on SMAD signaling. PLoS One 9, e93265.   DOI
26 Shu, Y. S., Tao, W., Miao, Q. B., Zhu, Y. B. and Yang, Y. F. (2014) Improvement of ventilation-induced lung injury in a rodent model by inhibition of inhibitory ${\kappa}B$ kinase. J. Trauma Acute. Care Surg. 76, 1417-1424.   DOI
27 Serhan, C. N., Hong, S., Gronert, K., Colgan, S. P., Devchand, P. R., Mirick, G. and Moussignac, R. L. (2002) Resolvins a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 196, 1025-1037.   DOI
28 Van Meeteren, L. A. and Ten Dijke, P. (2012) Regulation of endothelial cell plasticity by TGF-$\beta$. Cell Tissue Res. 347, 177-186.   DOI
29 Spite, M., Norling, L. V., Summers, L., Yang, R., Cooper, D., Petasis, N. A., Flower, R. J., Perretti, M. and Serhan, C. N. (2009) Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature 461, 1287-1291.   DOI
30 Thiery, J. P. (2003) Epithelial-mesenchymal transitions in development and pathologies. Curr. Opin. Cell Biol. 15, 740-746.   DOI
31 Wu, S. H., Zhang, Y. M., Tao, H. X. and Dong, L. (2010) Lipoxin A4 inhibits transition of epithelial to mesenchymal cells in proximal tubules. Am. J. Nephrol. 32, 122-136.   DOI
32 Xiao, L., Kim, D. J., Davis, C. L., McCann, J. V., Dunleavey, J. M., Vanderlinden, A. K., Xu, N., Pattenden, S. G., Frye, S. V., Xu, X., Onaitis, M., Monaghan-Benson, E., Burridge, K. and Dudley, A. C. (2015) Tumor endothelial cells with distinct patterns of $TGF{\beta}$- driven endothelial-to-mesenchymal transition. Cancer Res. 75, 1244-1254.   DOI
33 Yao, Y., Jumabay, M., Ly, A., Radparvar, M., Cubberly, M. R. and Boström, K. I. (2013) A role for the endothelium in vascular calcification. Circ. Res. 113, 495-504.   DOI
34 Yan, X., Liu, Z. and Chen, Y. (2009) Regulation of TGF-$\beta$ signaling by Smad7. Acta Biochim. Biophys. Sin. (Shanghai). 41, 263-272.   DOI
35 Zeisberg, E. M., Potenta, S., Xie, L., Zeisberg, M. and Kalluri, R. (2007) Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res. 67, 10123-10128.   DOI