Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2010

Open Access 01-12-2010 | Research

Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns

Authors: Dunja M Baston-Büst, Martin Götte, Wolfgang Janni, Jan-Steffen Krüssel, Alexandra P Hess

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

Login to get access

Abstract

Background

Successful embryonic implantation depends on a synchronized embryo-maternal dialogue. Chemokines, such as chemokine ligand 1 (CXCL1), play essential roles in the maternal reproductive tract leading to morphological changes during decidualization, mediating maternal acceptance towards the semi-allograft embryo and induction of angiogenesis. Chemokine binding to their classical G-protein coupled receptors is essentially supported by the syndecan (Sdc) family of heparan sulfate proteoglycans. The aim of this study was to identify the involvement of Sdc-1 at the embryo-maternal interface regarding changes of the chemokine and angiogenic profile of the decidua during the process of decidualization and implantation in human endometrium.

Methods

A stable Sdc-1 knock-down was generated in the immortalized human endometrial stromal cell line St-T1 and was named KdS1. The ability of KdS1 to decidualize was proven by Insulin-like growth factor binding 1 (IGFBP1) and prolactin (PRL) confirmation on mRNA level before further experiments were carried out. Dot blot protein analyses of decidualized knock-down cells vs non-transfected controls were performed. In order to imitate embryonic implantation, decidualized KdS1 were then incubated with IL-1beta, an embryo secretion product, vs controls. Statistical analyses were performed applying the Student's t-test with p < 0.05, p < 0.02 and p < 0.01 and one way post-hoc ANOVA test with p < 0.05 as cut-offs for statistical significance.

Results

The induction of the Sdc-1 knock-down revealed significant changes in cytokine and angiogenic factor expression profiles of dKdS1 vs decidualized controls. Incubation with embryonic IL-1beta altered the expression patterns of KdS1 chemokines and angiogenic factors towards inflammatory-associated molecules and factors involved in matrix regulation.

Conclusions

Sdc-1 knock-down in human endometrial stroma cells led to fulminant changes regarding cytokine and angiogenic factor expression profiles upon decidualization and imitation of embryonic contact. Sdc-1 appears to play an important role as a co-receptor and storage factor for many cytokines and angiogenic factors during decidualization and implantation period, supporting proper implantation and angiogenesis by regulation of chemokine and angiogenic factor secretion in favour of the implanting embryo.
Appendix
Available only for authorised users
Literature
1.
McEwan M, Lins RJ, Munro SK, Vincent ZL, Ponnampalam AP, Mitchell MD: Cytokine regulation during the formation of the fetal-maternal interface: Focus on cell-cell adhesion and remodelling of the extra-cellular matrix. Cytokine Growth factor Rev. 2009, 20: 241-249. 10.1016/j.cytogfr.2009.05.004.CrossRefPubMed
2.
Simon C, Frances A, Piquette G, Hendrickson M, Milki A, Polan ML: Interleukin-1 system in the materno-trophoblast unit in human implantation: immunohistochemical evidence for autocrine/paracrine function. J Clin Endocrinol Metab. 1994, 78: 847-854. 10.1210/jc.78.4.847.PubMed
3.
Engert S, Rieger L, Kapp M, Becker JC, Dietl J, Kämmerer U: Profiling chemokines, cytokines and growth factors in human early pregnancy decidua by protein array. Am J Reprod Immunol. 2007, 58: 129-137. 10.1111/j.1600-0897.2007.00498.x.CrossRefPubMed
4.
Fest S, Aldo PB, Abrahams VM, Visintin I, Alvero A, Chen R, Chavez SL, Romero R, Mor G: Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy. Am J Reprod Immunol. 2007, 57: 55-66. 10.1111/j.1600-0897.2006.00446.x.CrossRefPubMed
5.
6.
Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M, Nayak N, Genbecev-Krtolica O, Mavrogianis P, Ferrer K, Kruessel J, Fazleabas AT, Fisher SJ, Giudice LC: Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators. Biol Reprod. 2007, 76: 102-117. 10.1095/biolreprod.106.054791.CrossRefPubMed
7.
Popovici RM, Betzler NK, Krause MS, Luo M, Jauckus J, Germeyer A, Bloethner S, Schlotterer A, Kumar R, Strowitzki T, Wolff M: Gene Expression Profiling of Human Endometrial-Trophoblast Interaction in a Coculture Model. Endocrinology. 2006, 147: 5662-5675. 10.1210/en.2006-0916.CrossRefPubMed
8.
van der Voort R, Keehnen RMJ, Beuling EA, Spaargaren M, Pals ST: Regulation of Cytokine Signaling by B Cell Antigen Receptor and CD40-controlled Expression of Heparan Sulfate Proteoglycans. J Exp Med. 2000, 192: 1115-1124. 10.1084/jem.192.8.1115.PubMedCentralCrossRefPubMed
9.
Alexopoulou AN, Multhaupt HAB, Couchman JR: Syndecans in wound healing, inflammation and vascular biology. Int J Biochem Cell B. 2007, 39: 505-528. 10.1016/j.biocel.2006.10.014.CrossRef
10.
Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M: Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999, 68: 729-777. 10.1146/annurev.biochem.68.1.729.CrossRefPubMed
11.
Germeyer A, Klinkert MS, Huppertz AG, Clausmeyer S, Popovici RM, Strowitzki T, von Wolff M: Expression of syndecans, cell-cell interaction regulating heparan sulfate proteoglycans, within the human endometrium and their regulation throughout the menstrual cycle. Fertil Steril. 2007, 87: 657-663. 10.1016/j.fertnstert.2006.07.1526.CrossRefPubMed
12.
Jokimaa V, Inki P, Kujari H, Hirvonen O, Ekholm E, Anttila L: Expression of syndecan-1 in human placenta and decidua. Placenta. 1998, 19: 157-163. 10.1016/S0143-4004(98)90004-2.CrossRefPubMed
13.
Brosens JJ, Takeda S, Acevedo CH, Lewis MP, Kirby PL, Symes EK, Krausz T, Purohit A, Gellersen B, White J: Human endometrial fibroblasts immortalized by simian virus 40 large T antigen differentiate in response to a decidualization stimulus. Endocrinology. 1996, 137: 2225-2231. 10.1210/en.137.6.2225.PubMed
14.
Samalecos A, Reimann K, Wittmann S, Schulte HM, Brosens JJ, Bamberger AM, Gellersen B: Characterization of a novel telomerase-immortalized human endometrial stromal cell line, St-T1b. Reprod Biol Endocrinol. 2009, 7: 10.1186/1477-7827-7-76.
15.
Beauvais DM, Burbach BJ, Rapraeger AC: The syndecan-1 ectodomain regulates {alpha}v{beta}3 integrin activity in human mammary carcinoma cells. J Cell Biol. 2004, 167: 171-181. 10.1083/jcb.200404171.PubMedCentralCrossRefPubMed
16.
17.
18.
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987, 162: 156-159. 10.1016/0003-2697(87)90021-2.CrossRefPubMed
19.
Baston-Büst D, Hess A, Hirchenhain J, Krücken J, Wunderlich F, Krüssel JS, Friebe-Hoffmann U: A possible ambivalent role for relaxin in human myometrial and decidual cells in vitro. Arch Gyn Obstet. 2009, 280: 961-969. 10.1007/s00404-009-1046-8.CrossRef
20.
Yeung WSB, Ho PC, Lau EYL, Chan STH: Improved development of human embryos in vitro by a human oviductal cell co-culture system. Hum Reprod. 1992, 7: 1144-11499.PubMed
21.
Kienzle N, Young D, Zehntner S, Bushell G, Sculley T: DNaseI treatment is a prerequisite for the amplification of cDNA from episomal-based genes. Biotechniques. 1996, 20: 612-616.PubMed
22.
Guo CH, Koo CY, Bay BH, Tan PH, Yip G: Comparison of the effects of differentially sulphated bovine kidney- and porcine intestine-derived heparan sulphate on breast carcinoma cellular behaviour. Int J Oncol. 2007, 31: 1415-1423.PubMed
23.
Livak KJ, Schmittgen T: Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-[Delta][Delta]CT Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
24.
Issa R, Xie S, Lee KY, Stanbridge RD, Bhavsar P, Sukkar MB, Chung KF: GRO-{alpha} regulation in airway smooth muscle by IL-1beta and TNF-{alpha}: role of NF-{kappa}B and MAP kinases. Am J Physiol Lung Cell Mol Physiol. 2006, 291: L66-74. 10.1152/ajplung.00384.2005.CrossRefPubMed
25.
Götte M: Syndecans as modulators of chemokine function. Progress in chemokine research. Edited by: Linkes WP. 2007, Nova Science Publishers
26.
McDermott SP, Ranheim EA, Leatherberry VS, Khwaja SS, Klos KS, Alexander C: Juvenile syndecan-1 null mice are protected from carcinogen-induced tumor development. Oncogene. 2006, 26: 1407-1416. 10.1038/sj.onc.1209930.CrossRefPubMed
27.
Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, Dzuiba J, Van Damme J, Walz A, Marriott D, Chan SY, Roczniak S, Shanafelt AB: The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995, 270: 27348-27357. 10.1074/jbc.270.45.27348.CrossRefPubMed
28.
Ahuja S, Murphy P: The CXC chemokines growth-regulated oncogene (GRO) alpha, GROß, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor. J Biol Chem. 1996, 271: 20545-20550. 10.1074/jbc.271.34.20545.CrossRefPubMed
29.
Nasser MW, Raghuwanshi SK, Grant DJ, Jala VR, Rajarathnam K, Richardson R: Differential Activation and Regulation of CXCR1 and CXCR2 by CXCL8 Monomer and Dimer. J Immunol. 2009, 183: 3425-3432. 10.4049/jimmunol.0900305.PubMedCentralCrossRefPubMed
30.
Li Q, Park PW, Wilson CL, Parks WC: Matrilysin Shedding of Syndecan-1 Regulates Chemokine Mobilization and Transepithelial Efflux of Neutrophils in Acute Lung Injury. Cell. 2002, 111: 635-646. 10.1016/S0092-8674(02)01079-6.CrossRefPubMed
31.
Marshall LJ, Ramdin LSP, Brooks T, DPhil PC, Shute JK: Plasminogen Activator Inhibitor-1 Supports IL-8-Mediated Neutrophil Transendothelial Migration by Inhibition of the Constitutive Shedding of Endothelial IL-8/Heparan Sulfate/Syndecan-1 Complexes. J Immunol. 2003, 171: 2057-2065.CrossRefPubMed
32.
Oh JH, Kim JH, Ahn HJ, Yoon JH, Yoo SC, Choi DS, Lee IS, Ryu HS, Min C: Syndecan-1 enhances the endometrial cancer invasion by modulating matrix metalloproteinase-9 expression through nuclear factor [kappa]B. Gynecol Oncol. 2009, 114: 509-515. 10.1016/j.ygyno.2009.05.027.CrossRefPubMed
33.
Wanninger J, Neumeier M, Weigert J, Bauer S, Weiss TS, Schaffler A, Krempl C, Bleyl C, Aslanidis C, Scholmerich J, Buechler C: Adiponectin-stimulated CXCL8 release in primary human hepatocytes is regulated by ERK1/ERK2, p38 MAPK, NF-{kappa}B, and STAT3 signaling pathways. Am J Physiol Gastrointest Liver Physiol. 2009, 297: G611-618. 10.1152/ajpgi.90644.2008.CrossRefPubMed
34.
Wang B, Khachigian LM, Esau L, Birrer MJ, Zhao X, Parker MI, Hendricks DT: A Key Role for Early Growth Response-1 and Nuclear Factor-ΰB in Mediating and Maintaining GRO/CXCR2 Proliferative Signaling in Esophageal Cancer. Mol Cancer Res. 2009, 7: 755-764. 10.1158/1541-7786.MCR-08-0472.CrossRefPubMed
35.
Meter RA, Wira CR, Fahey J: Secretion of monocyte chemotactic protein-1 by human uterine epithelium directs monocyte migration in culture. Fertil Steril. 2005, 84: 191-201. 10.1016/j.fertnstert.2005.01.104.CrossRefPubMed
36.
Huang SJ, Schatz F, Masch R, Rahman M, Buchwalder L, Niven-Fairchild T, Tang C, Abrahams VM, Krikun G, Lockwood CJ: Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cells. J Reprod Immunol. 2006, 72: 60-73. 10.1016/j.jri.2006.03.002.CrossRefPubMed
37.
He YY, Du MR, Guo PF, He XJ, Zhou WH, Zhu XY, Li D: Regulation of C-C motif chemokine ligand 2 and its receptor in human decidual stromal cells by pregnancy-associated hormones in early gestation. Hum Reprod. 2007, 22: 2733-2742. 10.1093/humrep/dem208.CrossRefPubMed
38.
Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerle-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C: MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med. 2007, 13: 587-596. 10.1038/nm1567.CrossRefPubMed
39.
Kats R, Al-Akoum M, Guay S, Metz C, Akoum A: Cycle-dependent expression of macrophage migration inhibitory factor in the human endometrium. Hum Reprod. 2005, 20: 3518-3525. 10.1093/humrep/dei234.CrossRefPubMed
40.
Cao WG, Morin M, Metz C, Maheux R, Akoum A: Stimulation of Macrophage Migration Inhibitory Factor Expression in Endometrial Stromal Cells by Interleukin 1, beta Involving the Nuclear Transcription Factor NF-kappaB. Biol Reprod. 2005, 73: 565-570. 10.1095/biolreprod.104.038331.CrossRefPubMed
41.
Muramatsu T, Muramatsu H: Glycosaminoglycan-binding cytokines as tumor markers. PROTEOMICS. 2008, 8: 3350-3359. 10.1002/pmic.200800042.CrossRefPubMed
42.
Fitzgerald JS, Poehlmann TG, Schleussner E, Markert UR: Trophoblast invasion: the role of intracellular cytokine signalling via signal transducer and activator of transcription 3 (STAT3). Hum Reprod Update. 2008, 14: 335-344. 10.1093/humupd/dmn010.CrossRefPubMed
43.
Saito S, Sakakura S, Enomoto M, Ichijo M, Matsumoto K, Nakamura T: Hepatocyte Growth Factor Promotes the Growth of Cytotrophoblasts by the Paracrine Mechanism. J Biochem. 1995, 117: 671-676. 10.1093/jb/117.2.276.CrossRefPubMed
44.
Ohmichi H, Koshimizu U, Matsumoto K, Nakamura T: Hepatocyte growth factor (HGF) acts as a mesenchyme-derived morphogenic factor during fetal lung development. Development. 1998, 125: 1315-1324.PubMed
45.
Yoshida S, Harada T, Mitsunari M, Iwabe T, Sakamoto Y, Tsukihara S, Iba Y, Horie S, Terakawa N: Hepatocyte Growth Factor/Met System Promotes Endometrial and Endometriotic Stromal Cell Invasion via Autocrine and Paracrine Pathways. J Clin Endocrinol Metab. 2004, 89: 823-832. 10.1210/jc.2003-030874.CrossRefPubMed
46.
Derksen PWB, Keehnen RMJ, Evers LM, van Oers MHJ, Spaargaren M, Pals ST: Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma. Blood. 2002, 99: 1405-1410. 10.1182/blood.V99.4.1405.CrossRefPubMed
47.
Jin Y, Wang X, Xiao Y, Lv C, Ding C, Lin Q: The Role of TSP-1 on Decidual Macrophages Involved in the Susceptibility to Unexplained Recurrent Spontaneous Abortion. Am J Reprod Immunol. 2009, 61: 253-260. 10.1111/j.1600-0897.2009.00689.x.CrossRefPubMed
48.
Adams JC, Kureishy N, Taylor AL: A Role for Syndecan-1 in Coupling Fascin Spike Formation by Thrombospondin-1. J Cell Biol. 2001, 152: 1169-1182. 10.1083/jcb.152.6.1169.PubMedCentralCrossRefPubMed
49.
Laird SM, Dalton CF, Okon MA, Bunning RAD, Marshall R, Li TC: Metalloproteinases and tissue inhibitor of metalloproteinase 1 (TIMP-1) in endometrial flushings from pre- and post-menopausal women and from women with endometrial adenocarcinoma. J Reprod Fertil. 1999, 115: 225-232. 10.1530/jrf.0.1150225.CrossRefPubMed
50.
Rechtman MP, Zhang J, Salamonsen LA: Effect of inhibition of matrix metalloproteinases on endometrial decidualization and implantation in mated rats. J Reprod Fertil. 1999, 117: 169-177. 10.1530/jrf.0.1170169.CrossRefPubMed
51.
Nikolova V, Koo CY, Ibrahim SA, Wang Z, Spillmann D, Dreier R, Kelsch R, Fischgrabe J, Smollich M, Rossi LH, Sibrowski W, Wulfing P, Kiesel L, Yip GW, Gotte M: Differential roles for membrane-bound and soluble syndecan-1 (CD138) in breast cancer progression. Carcinogenesis. 2009, 30: 397-407. 10.1093/carcin/bgp001.CrossRefPubMed
52.
Bottazzi B, Garlanda C, Cotena A, Moalli F, Jaillon S, Deban L, Mantovani A: The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity. Immunol Rev. 2009, 227: 9-18. 10.1111/j.1600-065X.2008.00719.x.CrossRefPubMed
53.
Tranguch S, Chakrabarty A, Guo Y, Wang H, Dey SK: Maternal Pentraxin 3 Deficiency Compromises Implantation in Mice. Biol Reprod. 2007, 77: 425-432. 10.1095/biolreprod.107.062414.CrossRefPubMed
54.
Jaillon S, Jeannin P, Hamon Y, Fremaux I, Doni A, Bottazzi B, Blanchard S, Subra J-F, Chevailler A, Mantovani A, Delneste Y: Endogenous PTX3 translocates at the membrane of late apoptotic human neutrophils and is involved in their engulfment by macrophages. Cell Death Differ. 2008, 16: 465-474. 10.1038/cdd.2008.173.CrossRefPubMed
55.
Krüssel JS, Bielfeld P, Polan ML, Simón C: Regulation of embryonic implantation. Eur J Obstet Gynecol Reprod Biol. 2003, 110: S2-S9. 10.1016/S0301-2115(03)00167-2.CrossRefPubMed
56.
Boomsma CM, Kavelaars A, Eijkemans MJC, Amarouchi K, Teklenburg G, Gutknecht D, Fauser BJCM, Heijnen CJ, Macklon N: Cytokine profiling in endometrial secretions: a non-invasive window on endometrial receptivity. RBM Online. 2009, 18: 85-94.PubMed
57.
Rops AL, Gotte M, Baselmans MH, van den Hoven MJ, Steenbergen EJ, Lensen JF, Wijnhoven TJ, Cevikbas F, van den Heuvel LP, van Kuppevelt TH, Berden JH, van der Vlag J: Syndecan-1 deficiency aggravates anti-glomerular basement membrane nephritis. Kidney Int. 2007, 72: 1204-1215. 10.1038/sj.ki.5002514.CrossRefPubMed
58.
Gupta P, McCarthy J, Verfaillie C: Stromal fibroblast heparan sulfate is required for cytokine-mediated ex vivo maintenance of human long-term culture-initiating cells. Blood. 1996, 87: 3229-3236.PubMed
Metadata
Title
Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns
Authors
Dunja M Baston-Büst
Martin Götte
Wolfgang Janni
Jan-Steffen Krüssel
Alexandra P Hess
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-8-133

Other articles of this Issue 1/2010

Reproductive Biology and Endocrinology 1/2010 Go to the issue

Research

Swimming suppresses hepatic vitellogenesis in European female silver eels as shown by expression of the estrogen receptor 1, vitellogenin1 and vitellogenin2 in the liver

Research

The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers

Research

Arsenic abrogates the estrogen-signaling pathway in the rat uterus

Review

Reproductive outcome after hysteroscopic septoplasty in patients with septate uterus - a retrospective cohort study and systematic review of the literature

Research

Ovulation-inducing factor: a protein component of llama seminal plasma

Debate

Effects of luteectomy in early pregnancy on the maintenance of gestation and plasma progesterone concentrations in the viviparous temperate lizard Barisia imbricata imbricata