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Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Research Article

Proteome Profiling of Serum Exosomes from Newborns Delivered by Mothers with Preeclampsia

Author(s): Haiying Li, Xiaoqun Zhang, Xianhui Hong, Shuxuan Zhang, Haijun Tang, Jinlong Shi, Hui Peng* and Youjia Wu*

Volume 19, Issue 3, 2022

Published on: 10 May, 2022

Page: [281 - 288] Pages: 8

DOI: 10.2174/1570164619666220406121420

Price: $65

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Abstract

Background: Preeclampsia (PE) is a common pregnancy-specific disease with potential adverse maternal and neonatal outcomes.

Objective: We aimed to estimate proteomic profiles of serum-derived exosomes obtained from PE offspring with bioinformatics methods.

Methods: Serum samples were collected from 12 h, 24 h, and 72 h newborns delivered by preeclamptic and normal pregnant women. Exosomes were extracted, and the concentration and size distribution were determined. The exosome surface markers CD9, CD63, CD81, and TSG101, were assayed by Western blot. The exosome proteins were screened by quantitative proteomics with tandem mass tag (TMT). All the identified proteins were subjected to the Weighted Gene Co- Expression Network Analysis (WGCNA), GO function, and KEGG pathway analysis. A proteinprotein interaction network (PPI) was used to extract hub proteins through the Cytohubba plugin of Cytoscape.

Results: The extracted exosomes were round or oval vesicular structures at a 100-200 nm concentration, and the size distribution was standard and uniform. Exosome surface markers CD9, CD63, and CD81 were detected, and TSG101 was not detected. A total of 450 expressed proteins were selected, and 444 proteins were mapped with gene names. A blue module with 66 proteins highly correlated with phenotype at 12 h. Functional analyses revealed that module proteins were mainly enriched in the extracellular matrix. The top 10 selected hub proteins were identified as hub proteins, including COL6A2, HSPG2, COL4A1, COL3A1, etc.

Conclusion: Our study provides important information for exploring molecular mechanisms of preeclampsia and potential biomarkers for future diagnosis and treatment in the clinic.

Keywords: Preeclampsia, newborn, exosome, proteome, biomarker, WGCNA.

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[1]
Sutton, A.L.M.; Harper, L.M.; Tita, A.T.N. Hypertensive disorders in pregnancy. Obstet. Gynecol. Clin. North Am., 2018, 45(2), 333-347.
[http://dx.doi.org/10.1016/j.ogc.2018.01.012] [PMID: 29747734]
[2]
Fisher, S.J. Why is placentation abnormal in preeclampsia? Am. J. Obstet. Gynecol., 2015, 213(4)(Suppl.), S115-S122.
[http://dx.doi.org/10.1016/j.ajog.2015.08.042] [PMID: 26428489]
[3]
Backes, C.H.; Markham, K.; Moorehead, P.; Cordero, L.; Nankervis, C.A.; Giannone, P.J. Maternal preeclampsia and neonatal outcomes. J. Pregnancy, 2011, 2011, 214365.
[http://dx.doi.org/10.1155/2011/214365] [PMID: 21547086]
[4]
Graham, E.M.; Everett, A.D.; Delpech, J.C.; Northington, F.J. Blood biomarkers for evaluation of perinatal encephalopathy: State of the art. Curr. Opin. Pediatr., 2018, 30(2), 199-203.
[http://dx.doi.org/10.1097/MOP.0000000000000591] [PMID: 29346139]
[5]
Cappello, F.; Logozzi, M.; Campanella, C.; Bavisotto, C.C.; Marcilla, A.; Properzi, F.; Fais, S. Exosome levels in human body fluids: A tumor marker by themselves? Eur. J. Pharm. Sci., 2017, 96, 93-98.
[http://dx.doi.org/10.1016/j.ejps.2016.09.010] [PMID: 27640113]
[6]
Gowda, R.; Robertson, B.M.; Iyer, S.; Barry, J.; Dinavahi, S.S.; Robertson, G.P. The role of exosomes in metastasis and progression of melanoma. Cancer Treat. Rev., 2020, 85, 101975.
[http://dx.doi.org/10.1016/j.ctrv.2020.101975] [PMID: 32050108]
[7]
Langfelder, P.; Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics, 2008, 9(1), 559.
[http://dx.doi.org/10.1186/1471-2105-9-559] [PMID: 19114008]
[8]
Yu, G.; Wang, L.G.; Han, Y.; He, Q.Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5), 284-287.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[9]
Chin, C.H.; Chen, S.H.; Wu, H.H.; Ho, C.W.; Ko, M.T.; Lin, C.Y. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 2014, 8(S4), S11.
[http://dx.doi.org/10.1186/1752-0509-8-S4-S11] [PMID: 25521941]
[10]
Pathan, M.; Fonseka, P.; Chitti, S.V.; Kang, T.; Sanwlani, R.; Van Deun, J.; Hendrix, A.; Mathivanan, S. Vesiclepedia 2019: A compendi-um of RNA, proteins, lipids and metabolites in extracellular vesicles. Nucleic Acids Res., 2019, 47(D1), D516-D519.
[http://dx.doi.org/10.1093/nar/gky1029] [PMID: 30395310]
[11]
Kalra, H.; Simpson, R.J.; Ji, H.; Aikawa, E.; Altevogt, P.; Askenase, P.; Bond, V.C.; Borràs, F.E.; Breakefield, X.; Budnik, V.; Buzas, E.; Camussi, G.; Clayton, A.; Cocucci, E.; Falcon-Perez, J.M.; Gabrielsson, S.; Gho, Y.S.; Gupta, D.; Harsha, H.C.; Hendrix, A.; Hill, A.F.; In-al, J.M.; Jenster, G.; Krämer-Albers, E.M.; Lim, S.K.; Llorente, A.; Lötvall, J.; Marcilla, A.; Mincheva-Nilsson, L.; Nazarenko, I.; Nieu-wland, R.; Nolte-’t Hoen, E.N.; Pandey, A.; Patel, T.; Piper, M.G.; Pluchino, S.; Prasad, T.S.; Rajendran, L.; Raposo, G.; Record, M.; Reid, G.E.; Sánchez-Madrid, F.; Schiffelers, R.M.; Siljander, P.; Stensballe, A.; Stoorvogel, W.; Taylor, D.; Thery, C.; Valadi, H.; van Balkom, B.W.; Vázquez, J.; Vidal, M.; Wauben, M.H.; Yáñez-Mó, M.; Zoeller, M.; Mathivanan, S. Vesiclepedia: A compendium for extracellular vesicles with continuous community annotation. PLoS Biol., 2012, 10(12), e1001450.
[http://dx.doi.org/10.1371/journal.pbio.1001450] [PMID: 23271954]
[12]
Tranquilli, A.L.; Dekker, G.; Magee, L.; Roberts, J.; Sibai, B.M.; Steyn, W.; Zeeman, G.G.; Brown, M.A. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens., 2014, 4(2), 97-104.
[http://dx.doi.org/10.1016/j.preghy.2014.02.001] [PMID: 26104417]
[13]
Liong, S.; Oseghale, O.; To, E.E.; Brassington, K.; Erlich, J.R.; Luong, R.; Liong, F.; Brooks, R.; Martin, C.; O’Toole, S.; Vinh, A.; O’Neill, L.A.J.; Bozinovski, S.; Vlahos, R.; Papagianis, P.C.; O’Leary, J.J.; Brooks, D.A.; Selemidis, S. Influenza A virus causes maternal and fetal pathology via innate and adaptive vascular inflammation in mice. Proc. Natl. Acad. Sci. USA, 2020, 117(40), 24964-24973.
[http://dx.doi.org/10.1073/pnas.2006905117] [PMID: 32958663]
[14]
Romanowicz, L.; Jaworski, S.; Galewska, Z.; Gogiel, T. Separation and determination of fatty acids from lipid fractions by high-performance liquid chromatography: Cholesterol esters of umbilical cord arteries. Toxicol. Mech. Methods, 2008, 18(6), 509-513.
[http://dx.doi.org/10.1080/15376510701623912] [PMID: 19696943]
[15]
Kim, M.S.; Yu, J.H.; Lee, M.Y.; Kim, A.L.; Jo, M.H.; Kim, M.; Cho, S.R.; Kim, Y.H. Differential expression of extracellular matrix and adhesion molecules in fetal-origin amniotic epithelial cells of preeclamptic pregnancy. PLoS One, 2016, 11(5), e0156038.
[http://dx.doi.org/10.1371/journal.pone.0156038] [PMID: 27218821]
[16]
Sasse, P.; Malan, D.; Fleischmann, M.; Roell, W.; Gustafsson, E.; Bostani, T.; Fan, Y.; Kolbe, T.; Breitbach, M.; Addicks, K.; Welz, A.; Brem, G.; Hescheler, J.; Aszodi, A.; Costell, M.; Bloch, W.; Fleischmann, B.K. Perlecan is critical for heart stability. Cardiovasc. Res., 2008, 80(3), 435-444.
[http://dx.doi.org/10.1093/cvr/cvn225] [PMID: 18694874]
[17]
Kerever, A.; Mercier, F.; Nonaka, R.; de Vega, S.; Oda, Y.; Zalc, B.; Okada, Y.; Hattori, N.; Yamada, Y.; Arikawa-Hirasawa, E. Perlecan is required for FGF-2 signaling in the neural stem cell niche. Stem Cell Res. (Amst.), 2014, 12(2), 492-505.
[http://dx.doi.org/10.1016/j.scr.2013.12.009] [PMID: 24434631]
[18]
Johnson, M.P.; Fitzpatrick, E.; Dyer, T.D.; Jowett, J.B.; Brennecke, S.P.; Blangero, J.; Moses, E.K. Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach. Mol. Hum. Reprod., 2007, 13(1), 61-67.
[http://dx.doi.org/10.1093/molehr/gal095] [PMID: 17085769]
[19]
Yong, H.E.; Murthi, P.; Borg, A.; Kalionis, B.; Moses, E.K.; Brennecke, S.P.; Keogh, R.J. Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity. Placenta, 2014, 35(2), 117-124.
[http://dx.doi.org/10.1016/j.placenta.2013.11.008] [PMID: 24331737]
[20]
Oefner, C.M.; Sharkey, A.; Gardner, L.; Critchley, H.; Oyen, M.; Moffett, A. Collagen type IV at the fetal-maternal interface. Placenta, 2015, 36(1), 59-68.
[http://dx.doi.org/10.1016/j.placenta.2014.10.012] [PMID: 25465704]
[21]
Yong, H.E.; Murthi, P.; Wong, M.H.; Kalionis, B.; Brennecke, S.P.; Keogh, R.J. Anti-angiogenic collagen fragment arresten is increased from 16 weeks’ gestation in pre-eclamptic plasma. Placenta, 2015, 36(11), 1300-1309.
[http://dx.doi.org/10.1016/j.placenta.2015.08.013] [PMID: 26343951]
[22]
Kononikhin, A.S.; Zakharova, N.V.; Sergeeva, V.A.; Indeykina, M.I.; Starodubtseva, N.L.; Bugrova, A.E.; Muminova, K.T.; Khodzhaeva, Z.S.; Popov, I.A.; Shao, W.; Pedrioli, P.; Shmakov, R.G.; Frankevich, V.E.; Sukhikh, G.T.; Nikolaev, E.N. Differential diagnosis of preeclampsia based on urine peptidome features revealed by high resolution mass spectrometry. Diagnostics (Basel), 2020, 10(12), E1039.
[http://dx.doi.org/10.3390/diagnostics10121039] [PMID: 33287124]
[23]
Romanowicz, L.; Galewska, Z. Extracellular matrix remodeling of the umbilical cord in pre-eclampsia as a risk factor for fetal hyperten-sion. J. Pregnancy, 2011, 2011, 542695.
[http://dx.doi.org/10.1155/2011/542695] [PMID: 21490792]
[24]
Güzel, C.; van den Berg, C.B.; Koopman, S.; van Krugten, R.J.; Stoop, M.; Stingl, C.; Duvekot, J.J.; Luider, T.M. Cerebrospinal fluid of preeclamptic and normotensive pregnant women compared to nonpregnant women analyzed with mass spectrometry. ACS Omega, 2020, 5(50), 32256-32266.
[http://dx.doi.org/10.1021/acsomega.0c03910] [PMID: 33376863]
[25]
Zhang, H.; Xue, L.; Lv, Y.; Yu, X.; Zheng, Y.; Miao, Z.; Ding, H. Integrated microarray analysis of key genes and a miRNA mRNA regula-tory network of early onset preeclampsia. Mol. Med. Rep., 2020, 22(6), 4772-4782.
[http://dx.doi.org/10.3892/mmr.2020.11551] [PMID: 33173953]
[26]
Roediger, M.; Miosge, N.; Gersdorff, N. Tissue distribution of the laminin beta1 and beta2 chain during embryonic and fetal human de-velopment. J. Mol. Histol., 2010, 41(2-3), 177-184.
[http://dx.doi.org/10.1007/s10735-010-9275-5] [PMID: 20552257]
[27]
Guo, F.; Zhang, B.; Yang, H.; Fu, Y.; Wang, Y.; Huang, J.; Cheng, M.; Li, X.; Shen, Z.; Li, L.; He, P.; Xiang, A.P.; Wang, S.; Zhang, H. Systemic transcriptome comparison between early- And late-onset pre-eclampsia shows distinct pathology and novel biomarkers. Cell Prolif., 2021, 54(2), e12968.
[http://dx.doi.org/10.1111/cpr.12968] [PMID: 33332660]
[28]
Pan, H.T.; Guo, M.X.; Xiong, Y.M.; Ren, J.; Zhang, J.Y.; Gao, Q.; Ke, Z.H.; Xu, G.F.; Tan, Y.J.; Sheng, J.Z.; Huang, H.F. Differential pro-teomic analysis of umbilical artery tissue from preeclampsia patients, using iTRAQ isobaric tags and 2D nano LC-MS/MS. J. Proteomics, 2015, 112, 262-273.
[http://dx.doi.org/10.1016/j.jprot.2014.09.006] [PMID: 25234496]
[29]
Tan, KH; Tan, SS; Sze, SK; Lee, WK; Ng, MJ; Lim, SK Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. Am. J. Obstet. Gynecol., 2014, 211(4), 380 e1-13.
[30]
Tu, C.; Tao, F.; Qin, Y.; Wu, M.; Cheng, J.; Xie, M.; Shen, B.; Ren, J.; Xu, X.; Huang, D.; Chen, H. Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses. PeerJ, 2020, 8, e9753.
[http://dx.doi.org/10.7717/peerj.9753] [PMID: 32953262]

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