CXCL16 induces angiogenesis in autocrine signaling pathway involving hypoxia-inducible factor 1α in human umbilical vein endothelial cells

Yu,Xiaowen; Zhao,Renping; Lin,Sensen; Bai,Xianshu; Zhang,Luyong; Yuan,Shengtao; Sun,Li

doi:10.3892/or.2015.4520

CXCL16 induces angiogenesis in autocrine signaling pathway involving hypoxia-inducible factor 1α in human umbilical vein endothelial cells

Authors:
- Xiaowen Yu
- Renping Zhao
- Sensen Lin
- Xianshu Bai
- Luyong Zhang
- Shengtao Yuan
- Li Sun
View Affiliations

Affiliations: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China, Department of Biophysics, University of Saarland, D-66421 Homburg, Germany, Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China, Department of Molecular Physiology, University of Saarland, D-66421 Homburg, Germany
Published online on: December 24, 2015 https://doi.org/10.3892/or.2015.4520
Pages: 1557-1565

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chemokine (C-X-C motif) ligand 16 (CXCL16) is a new angiogenic factor inducing angiogenesis via extracellular signal-regulated kinases pathway. To further understand the molecular mechanism underlying CXCL16‑induced angiogenesis, we explored involvement of other relevant pathways in CXCL16-induced angiogenesis. In the present study, we investigated the mechanisms underlying CXCL16-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). CXCL16 promoted HUVEC proliferation, tube formation and migration. Enzyme-linked immunosorbent assay revealed that CXCL16 induced vascular endothelial growth factor secretion from HUVECs. Western blot analysis showed that CXCL16 increased the level of hypoxia‑inducible factor 1α, p-extracellular signal-regulated kinases (ERK), p-p38 and p-Akt dose- and time-dependently. ERK-, p38- and Akt-selective inhibitors significantly suppressed HUVEC proliferation, migration, tube formation and hypoxia-inducible factor 1α (HIF-1α) expression induced by CXCL16. Furthermore, CXCL16 peptides induced CXCL16 secretion via ERK, p38 and Akt pathways, which was suppressed by HIF-1α-selective inhibitor PX12. Our data suggest that CXCL16 induces angiogenesis in autocrine manner via ERK, Akt, p38 pathways and HIF-1α modulation.

View Figures

View References

1	Matloubian M, David A, Engel S, Ryan JE and Cyster JG: A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol. 1:298–304. 2000. View Article : Google Scholar
2	Shimaoka T, Kume N, Minami M, Hayashida K, Kataoka H, Kita T and Yonehara S: Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages. J Biol Chem. 275:40663–40666. 2000. View Article : Google Scholar : PubMed/NCBI
3	van der Voort R, van Lieshout AW, Toonen LW, Slöetjes AW, Van Den Berg WB, Figdor CG, Radstake TR and Adema GJ: Elevated CXCL16 expression by synovial macrophages recruits memory T cells into rheumatoid joints. Arthritis Rheum. 52:1381–1391. 2005. View Article : Google Scholar : PubMed/NCBI
4	Shimaoka T, Nakayama T, Kume N, Takahashi S, Yamaguchi J, Minami M, Hayashida K, Kita T, Ohsumi J, Yoshie O, et al: Cutting edge: SR-PSOX/CXC chemokine ligand 16 mediates bacterial phagocytosis by APCs through its chemokine domain. J Immunol. 171:1647–1651. 2003. View Article : Google Scholar : PubMed/NCBI
5	Heydtmann M, Lalor PF, Eksteen JA, Hubscher SG, Briskin M and Adams DH: CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver. J Immunol. 174:1055–1062. 2005. View Article : Google Scholar : PubMed/NCBI
6	Gao Q, Zhao YJ, Wang XY, Qiu SJ, Shi YH, Sun J, Yi Y, Shi JY, Shi GM, Ding ZB, et al: CXCR6 upregulation contributes to a proinflammatory tumor microenvironment that drives metastasis and poor patient outcomes in hepatocellular carcinoma. Cancer Res. 72:3546–3556. 2012. View Article : Google Scholar : PubMed/NCBI
7	Sung SY, Hsieh CL, Law A, Zhau HE, Pathak S, Multani AS, Lim S, Coleman IM, Wu LC, Figg WD, et al: Coevolution of prostate cancer and bone stroma in three-dimensional coculture: Implications for cancer growth and metastasis. Cancer Res. 68:9996–10003. 2008. View Article : Google Scholar : PubMed/NCBI
8	Hojo S, Koizumi K, Tsuneyama K, Arita Y, Cui Z, Shinohara K, Minami T, Hashimoto I, Nakayama T, Sakurai H, et al: High-level expression of chemokine CXCL16 by tumor cells correlates with a good prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer. Cancer Res. 67:4725–4731. 2007. View Article : Google Scholar : PubMed/NCBI
9	Shimaoka T, Nakayama T, Fukumoto N, Kume N, Takahashi S, Yamaguchi J, Minami M, Hayashida K, Kita T, Ohsumi J, et al: Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J Leukoc Biol. 75:267–274. 2004. View Article : Google Scholar
10	Gough PJ, Garton KJ, Wille PT, Rychlewski M, Dempsey PJ and Raines EW: A disintegrin and metalloproteinase 10-mediated cleavage and shedding regulates the cell surface expression of CXC chemokine ligand 16. J Immunol. 172:3678–3685. 2004. View Article : Google Scholar : PubMed/NCBI
11	Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N, Hartmann D, Sedlacek R, Dietrich S, Muetze B, et al: The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J Immunol. 172:6362–6372. 2004. View Article : Google Scholar : PubMed/NCBI
12	Lehrke M, Konrad A, Schachinger V, Tillack C, Seibold F, Stark R, Parhofer IG and Broedl UC: CXCL16 is a surrogate marker of inflammatory bowel disease. Scand J Gastroenterol. 43:283–288. 2008. View Article : Google Scholar : PubMed/NCBI
13	Ruth JH, Haas CS, Park CC, Amin MA, Martinez RJ, Haines GK, Shahrara S, Campbell PL and Koch AE: CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway. Arthritis Rheum. 54:765–778. 2006. View Article : Google Scholar : PubMed/NCBI
14	Postea O, Koenen RR, Hristov M, Weber C and Ludwig A: Homocysteine up-regulates vascular transmembrane chemokine CXCL16 and induces CXCR6⁺ lymphocyte recruitment in vitro and in vivo. J Cell Mol Med. 12:1700–1709. 2008. View Article : Google Scholar : PubMed/NCBI
15	Wang J, Lu Y, Koch AE, Zhang J and Taichman RS: CXCR6 induces prostate cancer progression by the AKT/mammalian target of rapamycin signaling pathway. Cancer Res. 68:10367–10376. 2008. View Article : Google Scholar : PubMed/NCBI
16	Lin S, Sun L, Hu J, Wan S, Zhao R, Yuan S and Zhang L: Chemo-kine C-X-C motif receptor 6 contributes to cell migration during hypoxia. Cancer Lett. 279:108–117. 2009. View Article : Google Scholar : PubMed/NCBI
17	Zhuge X, Murayama T, Arai H, Yamauchi R, Tanaka M, Shimaoka T, Yonehara S, Kume N, Yokode M and Kita T: CXCL16 is a novel angiogenic factor for human umbilical vein endothelial cells. Biochem Biophys Res Commun. 331:1295–1300. 2005. View Article : Google Scholar : PubMed/NCBI
18	Chandrasekar B, Bysani S and Mummidi S: CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation. J Biol Chem. 279:3188–3196. 2004. View Article : Google Scholar
19	Kwon KH, Ohigashi H and Murakami A: Dextran sulfate sodium enhances interleukin-1 beta release via activation of p38 MAPK and ERK1/2 pathways in murine peritoneal macrophages. Life Sci. 81:362–371. 2007. View Article : Google Scholar : PubMed/NCBI
20	Jiang BH, Zheng JZ, Aoki M and Vogt PK: Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc Natl Acad Sci USA. 97:1749–1753. 2000. View Article : Google Scholar : PubMed/NCBI
21	Binion DG, Otterson MF and Rafiee P: Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition. Gut. 57:1509–1517. 2008. View Article : Google Scholar : PubMed/NCBI
22	Zhu WH, Han J and Nicosia RF: Requisite role of p38 MAPK in mural cell recruitment during angiogenesis in the rat aorta model. J Vasc Res. 40:140–148. 2003. View Article : Google Scholar : PubMed/NCBI
23	Zhao R, Sun L, Lin S, Bai X, Yu B, Yuan S and Zhang L: The saponin monomer of dwarf lilyturf tuber, DT-13, inhibits angio-genesis under hypoxia and normoxia via multi-targeting activity. Oncol Rep. 29:1379–1386. 2013.PubMed/NCBI
24	Chi JT, Wang Z, Nuyten DS, Rodriguez EH, Schaner ME, Salim A, Wang Y, Kristensen GB, Helland Å, Børresen-Dale AL, et al: Gene expression programs in response to hypoxia: Cell type specificity and prognostic significance in human cancers. PLoS Med. 3:e472006. View Article : Google Scholar : PubMed/NCBI
25	Petering H, Kluthe C, Dulkys Y, Kiehl P, Ponath PD, Kapp A and Elsner J: Characterization of the CC chemokine receptor 3 on human keratinocytes. J Invest Dermatol. 116:549–555. 2001. View Article : Google Scholar : PubMed/NCBI
26	Zhou L, Sun L, Lin S, Fang D, Zhao R, Zhu J, Liu J, Chen L, Shi W, Yuan S, et al: Inhibition of angiogenic activity of hypoxic fibroblast cell line MRC-5 in vitro by topotecan. Med Oncol. 28:653–659. 2011. View Article : Google Scholar
27	Kim HG, Hwang YP and Jeong HG: Metallothionein-III induces HIF-1alpha-mediated VEGF expression in brain endothelial cells. Biochem Biophys Res Commun. 369:666–671. 2008. View Article : Google Scholar : PubMed/NCBI
28	Ahluwalia A and Tarnawski AS: Critical role of hypoxia sensor - HIF-1α in VEGF gene activation. Implications for angiogenesis and tissue injury healing. Curr Med Chem. 19:90–97. 2012. View Article : Google Scholar
29	Zubilewicz A, Hecquet C, Jeanny JC, Soubrane G, Courtois Y and Mascarelli F: Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: A comparative study with VEGF. Oncogene. 20:1403–1413. 2001. View Article : Google Scholar : PubMed/NCBI
30	Wang HQ, Bai L, Shen BR, Yan ZQ and Jiang ZL: Coculture with endothelial cells enhances vascular smooth muscle cell adhesion and spreading via activation of beta1-integrin and phosphatidylinositol 3-kinase/Akt. Eur J Cell Biol. 86:51–62. 2007. View Article : Google Scholar
31	Gee E, Milkiewicz M and Haas TL: p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress-induced angiogenesis. J Cell Physiol. 222:120–126. 2010. View Article : Google Scholar
32	Mavria G, Vercoulen Y, Yeo M, Paterson H, Karasarides M, Marais R, Bird D and Marshall CJ: ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell. 9:33–44. 2006. View Article : Google Scholar : PubMed/NCBI
33	Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, Simons JW and Semenza GL: Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: Implications for tumor angiogenesis and therapeutics. Cancer Res. 60:1541–1545. 2000.PubMed/NCBI
34	Treins C, Giorgetti-Peraldi S, Murdaca J, Semenza GL and Van Obberghen E: Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J Biol Chem. 277:27975–27981. 2002. View Article : Google Scholar : PubMed/NCBI
35	Stiehl DP, Jelkmann W, Wenger RH and Hellwig-Burgel T: Normoxic induction of the hypoxia-inducible factor 1alpha by insulin and interleukin-1beta involves the phosphatidylinositol 3-kinase pathway. FEBS Lett. 512:157–162. 2002. View Article : Google Scholar : PubMed/NCBI
36	Zheng X, Ruas JL, Cao R, Salomons FA, Cao Y, Poellinger L and Pereira T: Cell-type-specific regulation of degradation of hypoxia-inducible factor 1 alpha: Role of subcellular compartmentalization. Mol Cell Biol. 26:4628–4641. 2006. View Article : Google Scholar : PubMed/NCBI
37	Lai VK, Afzal MR, Ashraf M, Jiang S and Haider HK: Non-hypoxic stabilization of HIF-Ialpha during coordinated interaction between Akt and angiopoietin-1 enhances endothelial commitment of bone marrow stem cells. J Mol Med. 90:719–730. 2012. View Article : Google Scholar
38	Hur E, Chang KY, Lee E, Lee SK and Park H: Mitogen-activated protein kinase kinase inhibitor PD98059 blocks the trans-activation but not the stabilization or DNA binding ability of hypoxia-inducible factor-1alpha. Mol Pharmacol. 59:1216–1224. 2001.PubMed/NCBI
39	Roos TU, Heiss EH, Schwaiberger AV, Schachner D, Sroka IM, Oberan T, Vollmar AM and Dirsch VM: Caffeic acid phenethyl ester inhibits PDGF-induced proliferation of vascular smooth muscle cells via activation of p38 MAPK, HIF-1alpha, and heme oxygenase-1. J Nat Prod. 74:352–356. 2011. View Article : Google Scholar : PubMed/NCBI