Knockdown of P120 catenin aggravates endothelial injury under an impinging flow by inducing breakdown of adherens junctions

Zhao,Jian‑Lan; Xiao,Zhi‑Peng; Yu,Nian‑Zu; Jiang,Jin‑Wen; Li,Mei‑Hua

doi:10.3892/mmr.2018.9657

Knockdown of P120 catenin aggravates endothelial injury under an impinging flow by inducing breakdown of adherens junctions

Authors:
- Jian‑Lan Zhao
- Zhi‑Peng Xiao
- Nian‑Zu Yu
- Jin‑Wen Jiang
- Mei‑Hua Li
View Affiliations

Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China, Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China
Published online on: November 13, 2018 https://doi.org/10.3892/mmr.2018.9657
Pages: 541-548

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

At present, the mechanisms underlying intracranial aneurysm (IA) development remain unclear; however, hemodynamics is considered a crucial factor in the induction of IA. To elucidate the association between hemodynamics and endothelial cell (EC) functions, a modified T chamber system was designed to simulate the adjustable hemodynamic conditions of an artery bifurcation. Normal human umbilical vein ECs (HUVECs) and HUVECs with P120 catenin (P120ctn) knockdown were cultured on coverslips and placed in the chamber. A flow rate of 250 or 500 ml/min impinged on the cell layer. Subsequently, the expression levels of P120ctn and other proteins, and EC morphological alterations, were examined. In normal HUVECs, after 3 h under a flow rate of 500 ml/min, the expression levels of P120ctn, vascular endothelial (VE)‑Cadherin, Kaiso and α‑catenin were decreased, whereas matrix metalloproteinase‑2 (MMP‑2) was increased. In HUVECs with P120ctn knockdown, the period during which ECs adhered to the coverslip was reduced to 1 h under a flow rate of 500 ml/min. In addition, the expression levels of VE‑Cadherin, Kaiso and α‑catenin in ECs were decreased, whereas those of MMP‑2 were increased after 1 h; more prominent alterations were detected under a 500 ml/min flow rate compared with a 250 ml/min flow rate. Adherens junctions (AJs) are critical to the maintenance of normal morphology and EC functioning in the vascular wall, and P120ctn is an important regulator of AJs. Loss of P120ctn may be induced by hemodynamic alterations. In response to changes in hemodynamic conditions, a loss of P120ctn may aggravate AJs between ECs, thus inducing inflammation in the vascular wall. Clinically, hemodynamic alterations may result in a loss of P120ctn and endothelial injury; therefore, P120ctn may have a critical role in inducing intracranial aneurysms.

View Figures

View References

1	Li MH, Li PG, Huang QL and Ling J: Endothelial injury preceding intracranial aneurysm formation in rabbits. West Indian Med J. 63:167–171. 2014.PubMed/NCBI
2	Sakamoto N, Segawa K, Kanzaki M, Ohashi T and Sato M: Role of p120-catenin in the morphological changes of endothelial cells exposed to fluid shear stress. Biochem Biophys Res Commun. 398:426–432. 2010. View Article : Google Scholar : PubMed/NCBI
3	Huo Y, Wischgoll T and Kassab GS: Flow patterns in three-dimensional porcine epicardial coronary arterial tree. Am J Physiol Heart Circ Physiol. 293:H2959–H2970. 2007. View Article : Google Scholar : PubMed/NCBI
4	Szymanski MP, Metaxa E, Meng H and Kolega J: Endothelial cell layer subjected to impinging flow mimicking the apex of an arterial bifurcation. Ann Biomed Eng. 36:1681–1689. 2008. View Article : Google Scholar : PubMed/NCBI
5	Takeichi M: Morphogenetic roles of classic cadherins. Curr Opin Cell Biol. 7:619–627. 1995. View Article : Google Scholar : PubMed/NCBI
6	Giannotta M, Trani M and Dejana E: VE-cadherin and endothelial adherens junctions: Active guardians of vascular integrity. Dev Cell. 26:441–454. 2013. View Article : Google Scholar : PubMed/NCBI
7	Lagendijk AK and Hogan BM: VE-cadherin in vascular development: A coordinator of cell signaling and tissue morphogenesis. Curr Top Dev Biol. 112:325–352. 2015. View Article : Google Scholar : PubMed/NCBI
8	Madahian S, Navab KD, Pourtabatabaei N, Seyedali S, Safar S, Vazirian S and Hough G: Inflammation, high density lipoprotein and endothelium. Curr Med Chem. 21:2902–2909. 2014. View Article : Google Scholar : PubMed/NCBI
9	Perez-Moreno M, Song W, Pasolli HA, Williams SE and Fuchs E: Loss of p120 catenin and links to mitotic alterations, inflammation, and skin cancer. Proc Natl Acad Sci USA. 105:15399–15404. 2008. View Article : Google Scholar : PubMed/NCBI
10	O'Donnell JJ III, Zhuge Y, Holian O, Cheng F, Thomas LL, Forsyth CB and Lum H: Loss of p120 catenin upregulates transcription of pro-inflammatory adhesion molecules in human endothelial cells. Microvasc Res. 82:105–112. 2011. View Article : Google Scholar : PubMed/NCBI
11	Daniel JM and Reynolds AB: The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol Cell Biol. 19:3614–3623. 1999. View Article : Google Scholar : PubMed/NCBI
12	Pierre CC, Longo J, Mavor M, Milosavljevic SB, Chaudhary R, Gilbreath E, Yates C and Daniel JM: Kaiso overexpression promotes intestinal inflammation and potentiates intestinal tumorigenesis in Apc(Min/+) mice. Biochim Biophys Acta. 1852:1846–1855. 2015. View Article : Google Scholar : PubMed/NCBI
13	Zhao JL, Jia L, Wang XB, Zhang LL, Rong WL, Jiang JW and Li MH: Effects of adjustable impinging flow on the vascular endothelial cell layer in a modified T chamber. Int J Clin Exp Med. 10:62017.
14	Li MH, Zhang LL, Zhao JL, Wang XB and Rong WL: A fluid mechanics experimental device. Patent number: ZL 2014 2 0709792.5. Filed November 24, 2014; isssued, July 8, 2015.
15	Sharma PK: Mechanics of materials. Technol Health Care. 18:49–61. 2010.PubMed/NCBI
16	Walter C, Pabst A, Ziebart T, Klein M and Al-Nawas B: Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro. Oral Dis. 17:194–199. 2011. View Article : Google Scholar : PubMed/NCBI
17	Zhang J, O'Donnell JJ III, Holian O, Vincent PA, Kim KS and Lum H: P120 catenin represses transcriptional activity through Kaiso in endothelial cells. Microvasc Res. 80:233–239. 2010. View Article : Google Scholar : PubMed/NCBI
18	Meng H, Swartz DD, Wang Z, Hoi Y, Kolega J, Metaxa EM, Szymanski MP, Yamamoto J, Sauvageau E and Levy EI: A model system for mapping vascular responses to complex hemodynamics at arterial bifurcations in vivo. Neurosurgery. 59:1094–1101. 2006. View Article : Google Scholar : PubMed/NCBI
19	DePaola N, Gimbrone MA Jr, Davies PF and Dewey CF Jr: Vascular endothelium responds to fluid shear stress gradients. Arterioscler Thromb. 12:1254–1257. 1992. View Article : Google Scholar : PubMed/NCBI
20	Noren NK, Liu BP, Burridge K and Kreft B: p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol. 150:567–580. 2000. View Article : Google Scholar : PubMed/NCBI
21	Reynolds AB, Roesel DJ, Kanner SB and Parsons JT: Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol. 9:629–638. 1989. View Article : Google Scholar : PubMed/NCBI
22	Wang YL, Malik AB, Sun Y, Hu S, Reynolds AB, Minshall RD and Hu G: Innate immune function of the adherens junction protein p120-catenin in endothelial response to endotoxin. J Immunol. 186:3180–3187. 2011. View Article : Google Scholar : PubMed/NCBI
23	Ogden SR, Wroblewski LE, Weydig C, Romero-Gallo J, O'Brien DP, Israel DA, Krishna US, Fingleton B, Reynolds AB, Wessler S, et al: p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7. Mol Biol Cell. 19:4110–4121. 2008. View Article : Google Scholar : PubMed/NCBI