Angiotensin II inhibits the protein expression of ZO‑1 in vascular endothelial cells by downregulating VE‑cadherin

Liu,Longbin; Meng,Liping; Zhang,Peng; Lin,Hui; Chi,Jufang; Peng,Fang; Guo,Hangyuan

doi:10.3892/mmr.2018.8991

Angiotensin II inhibits the protein expression of ZO‑1 in vascular endothelial cells by downregulating VE‑cadherin

Authors:
- Longbin Liu
- Liping Meng
- Peng Zhang
- Hui Lin
- Jufang Chi
- Fang Peng
- Hangyuan Guo
View Affiliations

Affiliations: Department of Cardiology, Shaoxing Municipal Hospital, Shaoxing, Zhejiang 312000, P.R. China, Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China
Published online on: May 8, 2018 https://doi.org/10.3892/mmr.2018.8991
Pages: 429-434

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

Angiotensin II (Ang II) is reported to be involved in the development of various cardiovascular diseases by disrupting microvessel permeability, however, the underlying mechanism remains to be elucidated. The present study aimed to investigate the mechanism by which Ang II disrupts microvascular permeability. Rat endothelial cells were subjected to primary culture and identification. Cells in passages 4‑7 were then used for the following experiments. The cells were divided into control, Ang II, and Ang II + valsartan groups, and reverse transcription‑quantitative polymerase chain reaction and western blot analyses were perform to evaluate the expression of zonula occludens‑1 (ZO‑1) and vascular endothelial (VE)‑cadherin in the cells. The distribution of ZO‑1 protein was also detected using immunofluorescence assays. It was found that, compared with the control group, lower expression levels of ZO‑1 and VE‑cadherin were present in the Ang II group (P<0.01). ZO‑1 was also irregularly distributed at the periphery of the cells. In addition, the overexpression of VE‑cadherin reversed the effect of Ang II on the expression and distribution of ZO‑1 in endothelial cells. Together, these results suggested that Ang II inhibited the protein expression of ZO‑1 in vascular endothelial cells by downregulating VE‑cadherin, thus destroying the tight junctions between endothelial cells, which may also be the mechanism by which Ang II is involved in the development of cardiovascular diseases.

View Figures

View References

1	Bois Du P, Tortola Pablo C, Lodka D, Kny M, Schmidt F, Song K, Schmidt S, Bassel-Duby R, Olson EN and Fielitz J: Angiotensin II induces skeletal muscle atrophy by activating TFEB-mediated MuRF1 expression. Circ Res. 117:424–436. 2015. View Article : Google Scholar : PubMed/NCBI
2	Iwai M, Chen R, Li Z, Shiuchi T, Suzuki J, Ide A, Tsuda M, Okumura M, Min LJ, Mogi M and Horiuchi M: Deletion of angiotensin II type 2 receptor exaggerated atherosclerosis in apolipoprotein E-null mice. Circulation. 112:1636–1643. 2005. View Article : Google Scholar : PubMed/NCBI
3	Jones A, Deb R, Torsney E, Howe F, Dunkley M, Gnaneswaran Y, Gaze D, Nasr H, Loftus IM, Thompson MM and Cockerill GW: Rosiglitazone reduces the development and rupture of experimental aortic aneurysms. Circulation. 119:3125–3146. 2009. View Article : Google Scholar : PubMed/NCBI
4	Qi Z, Li Z, Hao D, Wang T, Xia Y, Sun T, Wang J, Zhuang F and Wang X: Association between angiopoietin-2 and enterovirus 71 induced pulmonary edema. Indian J Pediatr. 83:391–396. 2016. View Article : Google Scholar : PubMed/NCBI
5	Wu Z, Liu H, Ren W, Dai F, Chang J and Li B: VE-cadherin involved in the pulmonary microvascular endothelial cell barrier injury induced by angiotensin II through modulating the cellular apoptosis and skeletal rearrangement. Am J Transl Res. 8:4310–4319. 2016.PubMed/NCBI
6	Yamamoto T, Harada N, Kano K, Taya S, Canaani E, Matsuura Y, Mizoguchi A, Ide C and Kaibuchi K: The Ras target AF-6 interacts with ZO-1 and serves as a peripheral component of tight junctions in epithelial cells. J Cell Biol. 139:785–795. 1997. View Article : Google Scholar : PubMed/NCBI
7	Su L, Mruk DD, Lui WY, Lee WM and Cheng CY: P-glycoprotein regulates blood-testis barrier dynamics via its effects on the occludin/zonula occludens 1 (ZO-1) protein complex mediated by focal adhesion kinase (FAK). Proc Natl Acad Sci USA. 108:19623–19628. 2011. View Article : Google Scholar : PubMed/NCBI
8	Brinkmann BF, Steinbacher T, Hartmann C, Kummer D, Pajonczyk D, Mirzapourshafiyi F, Nakayama M, Weide T, Gerke V and Ebnet K: VE-cadherin interacts with cell polarity protein Pals1 to regulate vascular lumen formation. Mol Biol Cell. 27:2811–2821. 2016. View Article : Google Scholar : PubMed/NCBI
9	Iden S, Rehder D, August B, Suzuki A, Wolburg-Buchholz K, Wolburg H, Ohno S, Behrens J, Vestweber D and Ebnet K: A distinct PAR complex associates physically with VE-cadherin in vertebrate endothelial cells. EMBO Rep. 7:1239–1246. 2006. View Article : Google Scholar : PubMed/NCBI
10	Zhou J, Xi Y, Mu X, Zhao R, Chen H, Zhang L, Wu Y and Li Q: Antitumor immunity induced by VE-cadherin modified DC vaccine. Oncotarget. 8:67369–67379. 2017.PubMed/NCBI
11	Li S, Ai N, Shen M, Dang Y, Chong CM, Pan P, Kwan YW, Chan SW, Leung GPH, Hoi MPM, et al: Discovery of a ROCK inhibitor, FPND, which prevents cerebral hemorrhage through maintaining vascular integrity by interference with VE-cadherin. Cell Death Discov. 3:170512017. View Article : Google Scholar : PubMed/NCBI
12	Ji Z, Zhao F, Meng LP, Zhou CZ, Tang WL, Xu FK, Liu LB, Lv HT, Chi JF, Peng F and Guo HY: Chinese yellow wine inhibits production of matrixmetalloproteinase-2 induced by homocysteine in rat vascular endothelial cells. Int J Clin Exp Med. 9:838–852. 2016.
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Mogielnicki A, Chabielska E, Pawlak R, Szemraj J and Buczko W: Angiotensin II enhances thrombosis development in renovascular hypertensive rats. Thromb Haemost. 93:1069–1076. 2005.PubMed/NCBI
15	Du J, Leng J, Zhang L, Bai G, Yang D, Lin H and Qin J: Angiotensin II-induced apoptosis of human umbilical vein endothelial cells was inhibited by blueberry anthocyanin through bax- and Caspase 3-dependent pathways. Med Sci Monit. 22:3223–3228. 2016. View Article : Google Scholar : PubMed/NCBI
16	Zhao F, Ji Z, Chi J, Tang W, Zhai X, Meng L and Guo H: Effects of Chinese yellow wine on nitric oxide synthase and intercellular adhesion molecule-1 expressions in rat vascular endothelial cells. Acta Cardiol. 71:27–34. 2016. View Article : Google Scholar : PubMed/NCBI
17	Gurnik S, Devraj K, Macas J, Yamaji M, Starke J, Scholz A, Sommer K, Di Tacchio M, Vutukuri R, Beck H, et al: Angiopoietin-2-induced blood-brain barrier compromise and increased stroke size are rescued by VE-PTP-dependent restoration of Tie2 signaling. Acta Neuropathol. 131:753–773. 2016. View Article : Google Scholar : PubMed/NCBI
18	Yu N, Wang Z, Chen Y, Yang J, Lu X, Guo Y, Chen Z and Xu Z: The ameliorative effect of bloodletting puncture at hand twelve Jing-well points on cerebral edema induced by permanent middle cerebral ischemia via protecting the tight junctions of the blood-brain barrier. BMC Complement Altern Med. 17:4702017. View Article : Google Scholar : PubMed/NCBI
19	Chang C, Liu H, Wei C, Chang L, Liang J, Bei H, Li H, Liu S and Wu Y: Tongxinluo regulates expression of tight junction proteins and alleviates endothelial cell monolayer hyperpermeability via ERK-1/2 signaling pathway in oxidized low-density lipoprotein-induced human umbilical vein endothelial cells. Evid Based Complement Altern Med. 2017:41984862017. View Article : Google Scholar
20	Furuse M, Fujita K, Hiiragi T, Fujimoto K and Tsukita S: Claudin-1 and −2: Novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 141:1539–1550. 1998. View Article : Google Scholar : PubMed/NCBI
21	Stevenson BR, Siliciano JD, Mooseker MS and Goodenough DA: Identification of ZO-1: A high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol. 103:755–766. 1986. View Article : Google Scholar : PubMed/NCBI
22	Fredriksson-Lidman K, Van Itallie CM, Tietgens AJ and Anderson JM: Sorbin and SH3 domain-containing protein 2 (SORBS2) is a component of the acto-myosin ring at the apical junctional complex in epithelial cells. PLoS One. 12:e01854482017. View Article : Google Scholar : PubMed/NCBI
23	Ruan YC, Wang Y, Da Silva N, Kim B, Diao RY, Hill E, Brown D, Chan HC and Breton S: CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway. J Cell Sci. 127:4396–4408. 2014. View Article : Google Scholar : PubMed/NCBI
24	Sommers CL, Byers SW, Thompson EW, Torri JA and Gelmann EP: Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res Treat. 31:325–335. 1994. View Article : Google Scholar : PubMed/NCBI
25	Li N, Lee WM and Cheng CY: Overexpression of plastin 3 in Sertoli cells disrupts actin microfilament bundle homeostasis and perturbs the tight junction barrier. Spermatogenesis. 6:e12063532016. View Article : Google Scholar : PubMed/NCBI
26	Guo J, Cai H, Zheng J, Liu X, Liu Y, Ma J, Que Z, Gong W, Gao Y, Tao W and Xue Y: Long non-coding RNA NEAT1 regulates permeability of the blood-tumor barrier via miR-181d-5p-mediated expression changes in ZO-1, occludin, and claudin-5. Biochim Biophys Acta. 1863:2240–2254. 2017. View Article : Google Scholar : PubMed/NCBI
27	Wei SC, Yang-Yen HF, Tsao PN, Weng MT, Tung CC, Yu LCH, Lai LC, Hsiao JH, Chuang EY, Shun CT, et al: SHANK3 regulates intestinal barrier function through modulating ZO-1 expression through the PKCε-dependent pathway. Inflamm Bowel Dis. 23:1730–1740. 2017. View Article : Google Scholar : PubMed/NCBI
28	Priest AV, Shafraz O and Sivasankar S: Biophysical basis of cadherin mediated cell-cell adhesion. Exp Cell Research. 358:10–13. 2017. View Article : Google Scholar
29	Delgado-Bellido D, Serrano-Saenz S, Fernández-Cortés M and Oliver FJ: Vasculogenic mimicry signaling revisited: Focus on non-vascular VE-cadherin. Mol Cancer. 16:652017. View Article : Google Scholar : PubMed/NCBI
30	Zhang R and Ge J: Proteinase-activated receptor-2 modulates Ve-cadherin expression to affect human vascular endothelial barrier function. J Cell Biochem. 118:4587–4593. 2017. View Article : Google Scholar : PubMed/NCBI
31	Sauteur L, Affolter M and Belting HG: Distinct and redundant functions of Esama and VE-cadherin during vascular morphogenesis. Development. 144:1554–1565. 2017. View Article : Google Scholar : PubMed/NCBI
32	Liu W, Lv C, Zhang B, Zhou Q and Cao Z: MicroRNA-27b functions as a new inhibitor of ovarian cancer-mediated vasculogenic mimicry through suppression of VE-cadherin expression. RNA. 23:1019–1027. 2017. View Article : Google Scholar : PubMed/NCBI
33	Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, Potente M, Daly C, Dimmeler S and Dejana E: Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol. 10:923–934. 2008. View Article : Google Scholar : PubMed/NCBI
34	Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C and Dejana E: Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J Cell Biol. 174:593–604. 2006. View Article : Google Scholar : PubMed/NCBI
35	Gaengel K, Niaudet C, Hagikura K, Laviña B, Muhl L, Hofmann JJ, Ebarasi L, Nyström S, Rymo S, Chen LL, et al: The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev Cell. 23:587–599. 2012. View Article : Google Scholar : PubMed/NCBI
36	Komarova YA, Huang F, Geyer M, Daneshjou N, Garcia A, Idalino L, Kreutz B, Mehta D and Malik AB: VE-cadherin signaling induces EB3 phosphorylation to suppress microtubule growth and assemble adherens junctions. Mol Cell. 48:914–925. 2012. View Article : Google Scholar : PubMed/NCBI