A novel regulator of human villous trophoblast fusion: The Krüppel-like factor 6

Molecular Human Reproduction

Volumn 21, Issue 4, 2014, Pages 347-358

  Racca, Ana Cristina ^a   Ridano, Magali Evelin ^a   Camolotto, Soledad ^a   Genti Raimondi, Susana ^a   Panzetta Dutari, Graciela María ^a  

^a UNIVERSIDAD NACIONAL DE CÓRDOBA   (Argentina)

Author keywords

Cell fusion; Gene expression; Human trophoblast; Syncytin 1; Transcription factors

Indexed keywords

CHORIONIC GONADOTROPIN BETA SUBUNIT; CONNEXIN 43; KRUPPEL LIKE FACTOR 6; PLASMID DNA; PROTEIN; PROTEIN P21; SMALL INTERFERING RNA; SYNCYTIN 1 PROTEIN; UNCLASSIFIED DRUG; ZONULA OCCLUDENS PROTEIN; CDKN1A PROTEIN, HUMAN; CYCLIN DEPENDENT KINASE INHIBITOR 1A; KLF6 PROTEIN, HUMAN; KRUPPEL LIKE FACTOR; ONCOPROTEIN; PLACENTA PROTEIN; PROTEIN ZO1; SYNCYTIN; SYNCYTIN 2 PROTEIN, HUMAN; VIRUS ENVELOPE PROTEIN;

ARTICLE; CELL DIFFERENTIATION; CELL FUSION; CYTOTROPHOBLAST; DOWN REGULATION; FEMALE; GENE SILENCING; HUMAN; HUMAN CELL CULTURE; HUMAN TISSUE; IMMUNOFLUORESCENCE MICROSCOPY; PLACENTA; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SYNCYTIOTROPHOBLAST; VILLOUS CYTOTROPHOBLAST; WESTERN BLOTTING; ADULT; ANTAGONISTS AND INHIBITORS; CHORION VILLUS; CYTOLOGY; GENE EXPRESSION REGULATION; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PREGNANCY; PRIMARY CELL CULTURE; TROPHOBLAST;

MURINAE;

ADULT; CELL FUSION; CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN; CHORIONIC VILLI; CONNEXIN 43; CYCLIN-DEPENDENT KINASE INHIBITOR P21; FEMALE; GENE EXPRESSION REGULATION; GENE PRODUCTS, ENV; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; PREGNANCY; PREGNANCY PROTEINS; PRIMARY CELL CULTURE; PROTO-ONCOGENE PROTEINS; RNA, SMALL INTERFERING; TROPHOBLASTS; ZONULA OCCLUDENS-1 PROTEIN;

EID: 84926454031     PISSN: 13609947     EISSN: 14602407     Source Type: Journal    
DOI: 10.1093/molehr/gau113     Document Type: Article

References (62)

1. Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 2009;9:400-414.
2. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, MillerW, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997;25:3389-3402.
3. Andreoli V, Gehrau RC, Bocco JL. Biology of Kruppel-like factor 6 transcriptional regulator in cell life and death. IUBMB Life 2010;62:896-905.
4. Baczyk D, Drewlo S, Proctor L, Dunk C, Lye S, Kingdom J. Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast. Cell Death Differ 2009;16:719-727.
5. Benzeno S, Narla G, Allina J, Cheng GZ, Reeves HL, Banck MS, Odin JA, Diehl JA, Germain D, Friedman SL. Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1. Cancer Res 2004;64:3885-3891.
6. Bersinger NA, Odegard RA. Second- and third-trimester serum levels of placental proteins in preeclampsia and small-for-gestational age pregnancies. Acta Obstet Gynecol Scand 2004;83:37-45.
7. Blaise S, de Parseval N, Benit L, Heidmann T. Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci USA 2003; 100:13013-13018.
8. Botella LM, Sanchez-ElsnerT, Sanz-Rodriguez F,Kojima S, Shimada J,Guerrero-Esteo M, Cooreman MP, Ratziu V, Langa C, Vary CP et al. Transcriptional activation of endoglin and transforming growth factor-beta signaling components by cooperative interaction between Sp1 and KLF6: their potential rolein the response to vascular injury. Blood 2002;100:4001-4010.
9. Camolotto S, Racca A, Rena V, Nores R, Patrito LC, Genti-Raimondi S, Panzetta-Dutari GM. Expression and transcriptional regulation of individual pregnancy-specific glycoprotein genes in differentiating trophoblast cells. Placenta 2010;31:312-319.
10. Castellucci M, Kaufmann P. Basic Structure of the Villous Trees. In:Benirschke K, Kaufman P, Baergen RN (eds). Pathology of the Human Placenta, 5th edn. New York, NY: Springer, 2006, 50-120.
11. Chen PY, Yen JH, Kao RH, Chen JH. Down-regulation of the oncogene PTTG1 via the KLF6 tumor suppressor during induction of myeloid differentiation. PLoS ONE 2013;8:e71282.
12. Dunk CE, Gellhaus A, Drewlo S, Baczyk D, Potgens AJ, Winterhager E, Kingdom JC, Lye SJ. The molecular role of connexin 43 in human trophoblast cell fusion. Biol Reprod 2012;86:115.
13. Flores-Martin J, Rena V, Marquez S, Panzetta-Dutari GM, Genti-Raimondi S. StarD7 knockdown modulates ABCG2 expression, cell migration, proliferation, and differentiation of human choriocarcinoma JEG-3 cells. PLoS ONE 2012;7:e44152.
14. Fradet S, Pierredon S, Ribaux P, Epiney M, Shin Ya K, Irion O, Cohen M. Involvement of membrane GRP78 in trophoblastic cell fusion. PLoS ONE 2012;7:e40596.
15. Frendo JL, Vidaud M, Guibourdenche J, Luton D, Muller F, Bellet D, Giovagrandi Y, Tarrade A, Porquet D, Blot P et al. Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome. J Clin Endocrinol Metab 2000;85:3700-3707.
16. Frendo JL, Cronier L, Bertin G, Guibourdenche J, Vidaud M, Evain-Brion D, Malassine A. Involvement of connexin 43 in human trophoblast cell fusion and differentiation. J Cell Sci 2003a;116:3413-3421.
17. Frendo JL, Olivier D, Cheynet V, Blond JL, Bouton O, Vidaud M, Rabreau M, Evain-Brion D, Mallet F. Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Mol Cell Biol 2003b; 23:3566-3574.
18. Gauster M, Moser G, Orendi K, Huppertz B. Factors involved in regulating trophoblast fusion: potential role in the development of preeclampsia. Placenta 2009;30(Suppl. A):S49-S54.
19. Gehrau RC, D'Astolfo DS, Dumur CI, Bocco JL, Koritschoner NP. Nuclear expression of KLF6 tumor suppressor factor is highly associated with overexpression of ERBB2 oncoprotein in ductal breast carcinomas. PLoS ONE 2010;5:e8929.
20. Genbacev O, McMaster MT, Fisher SJ. A repertoire of cell cycle regulators whose expression is coordinated with human cytotrophoblast differentiation. Am J Pathol 2000;157:1337-1351.
21. Handwerger S. New insights into the regulation of human cytotrophoblast cell differentiation. Mol Cell Endocrinol 2010;323:94-104.
22. Handwerger S, Kessler CA. Transcription factor Ets1 regulates human cytotrophoblast cell differentiation. Endocr Rev 2013;34:MON-509.
23. Hubert MA, Sherritt SL, Bachurski CJ, Handwerger S. Involvement of transcription factor NR2F2 in human trophoblast differentiation. PLoS ONE 2010;5:e9417.
24. Huppertz B, Gauster M. Trophoblast fusion. Adv Exp Med Biol 2011; 713:81-95.
25. Ji L, Brkic J, Liu M, Fu G, Peng C, Wang YL. Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia. Mol Aspects Med 2013;34:981-1023.
26. Kao LC, Caltabiano S, Wu S, Strauss JF 3rd, Kliman HJ. The human villous cytotrophoblast: interactions with extracellular matrix proteins, endocrine function, and cytoplasmic differentiation in the absence of syncytium formation. Dev Biol 1988;130:693-702.
27. Kliman HJ, Nestler JE, Sermasi E, Sanger JM, Strauss JF 3rd. Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology 1986;118:1567-1582.
28. Knofler M, Saleh L, Bauer S, Vasicek R, Griesinger G, Strohmer H, Helmer H, Husslein P. Promoter elements and transcription factors involved in differentiation-dependent human chorionic gonadotrophin-alpha messenger ribonucleic acid expression of term villous trophoblasts. Endocrinology 2000;141:3737-3748.
29. Korgun ET,Celik-Ozenci C, Acar N, Cayli S, DesoyeG, Demir R. Location of cell cycle regulators cyclin B1, cyclin A,PCNA,Ki67 and cell cycle inhibitors p21, p27 and p57 in human first trimester placenta and deciduas. Histochem Cell Biol 2006;125:615-624.
30. Kremer-Tal S, Narla G, Chen Y, Hod E, DiFeo A, Yea S, Lee JS, Schwartz M, Thung SN, Fiel IM et al. Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates proliferation while reducing differentiation. J Hepatol 2007;46:645-654.
31. Kudo Y, Boyd CA, Sargent IL, Redman CW. Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia. Biochim Biophys Acta 2003; 1638:63-71.
32. Langbein M, Strick R, Strissel PL, VogtN, Parsch H, BeckmannMW, Schild RL. Impaired cytotrophoblast cell-cell fusion is associated with reduced syncytin and increased apoptosis in patients with placental dysfunction. Mol Reprod Dev 2008;75:175-183.
33. Larsson LI, Bjerregaard B, Talts JF. Cell fusions in mammals. Histochem Cell Biol 2008;129:551-561.
34. Li D, Yea S, Dolios G, Martignetti JA, Narla G, Wang R, Walsh MJ, Friedman SL. Regulation of Kruppel-like factor 6 tumor suppressor activity by acetylation. Cancer Res 2005a;65:9216-9225.
35. Li D, Yea S, Li S, Chen Z, Narla G, Banck M, Laborda J, Tan S, Friedman JM, Friedman SL et al. Kruppel-like factor-6 promotes preadipocyte differentiation through histone deacetylase 3-dependent repression of DLK1. J Biol Chem 2005b;280:26941-26952.
36. Liang CY,Wang LJ, Chen CP, Chen LF, Chen YH, Chen H. GCM1 regulation of the expression of syncytin 2 and its cognate receptor MFSD2A in human placenta. Biol Reprod 2010;83:387-395.
37. Lin L, Xu B, Rote NS. The cellular mechanism by which the human endogenous retrovirus ERV-3 env gene affects proliferation and differentiation in a human placental trophoblast model, BeWo. Placenta 2000;21:73-78.
38. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001;25:402-408.
39. Loregger T, Pollheimer J, Knofler M. Regulatory transcription factors controlling function and differentiation of human trophoblast--a review. Placenta 2003;24(Suppl. A):S104-S110.
40. Malassine A, Frendo JL, Evain-Brion D. Trisomy 21- affected placentas highlight prerequisite factors for human trophoblast fusion and differentiation. Int J Dev Biol 2010;54:475-482.
41. Matsumoto N, Kubo A, Liu H, Akita K, Laub F, Ramirez F, Keller G, Friedman SL. Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6. Blood 2006;107:1357-1365.
42. McConnell BB, Yang VW. Mammalian Kruppel-like factors in health and diseases. Physiol Rev 2010;90:1337-1381.
43. Mi S, Lee X, Li X, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang XY, Edouard P, Howes S et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 2000; 403:785-789.
44. Nakamura H, Chiambaretta F, Sugar J, Sapin V, Yue BY. Developmentally regulated expression of KLF6 in the mouse cornea and lens. Invest Ophthalmol Vis Sci 2004;45:4327-4332.
45. Narla G, Heath KE, Reeves HL, Li D, Giono LE, Kimmelman AC, Glucksman MJ, Narla J, Eng FJ, Chan AM et al. KLF6, a candidate tumor suppressor gene mutated in prostate cancer. Science 2001; 294:2563-2566.
46. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B. The choriocarcinoma cell line BeWo: syncytial fusion and expression of syncytium-specific proteins. Reproduction 2010;140:759-766.
47. Oren-Suissa M, Podbilewicz B. Cell fusion during development. Trends Cell Biol 2007;17:537-546.
48. Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ. p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science 1995;267:1024-1027.
49. Pidoux G, Gerbaud P, Cocquebert M, Segond N, Badet J, Fournier T, Guibourdenche J, Evain-Brion D. Review: Human trophoblast fusion and differentiation: lessons from trisomy 21 placenta. Placenta 2012; 33(Suppl):S81-S86.
50. Pidoux G, Gerbaud P, Gnidehou S, Grynberg M, Geneau G, Guibourdenche J, Carette D, Cronier L, Evain-Brion D, Malassine A et al. ZO-1 is involved in trophoblastic cell differentiation in human placenta. Am J Physiol Cell Physiol 2010;298:C1517-C1526.
51. Racca AC, Camolotto SA, Ridano ME, Bocco JL, Genti-Raimondi S, Panzetta-Dutari GM. Krüppel-like factor 6 expression changes during trophoblast syncytialization and transactivates bhcg and psg placental genes. PLoS ONE 2011;6:e22438.
52. Rama S, Suresh Y, Rao AJ. TGF beta1 induces multiple independent signals to regulate human trophoblastic differentiation: mechanistic insights. Mol Cell Endocrinol 2003;206:123-136.
53. Ruebner M, Strissel PL, Langbein M, Fahlbusch F, Wachter DL, Faschingbauer F, Beckmann MW, Strick R. Impaired cell fusion and differentiation in placentae from patients with intrauterine growth restriction correlate with reduced levels of HERV envelope genes. J Mol Med (Berl) 2010;88:1143-1156.
54. Schaiff WT, Carlson MG, Smith SD, Levy R, Nelson DM, Sadovsky Y. Peroxisome proliferator-activated receptor-gamma modulates differentiation of human trophoblast in a ligand-specific manner. J Clin Endocrinol Metab 2000;85:3874-3881.
55. Slavin DA, Koritschoner NP, Prieto CC, Lopez-Diaz FJ, Chatton B, Bocco JL. A new role for the Kruppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function. Oncogene 2004;23:8196-8205.
56. Vargas A, Moreau J, Landry S, LeBellego F, Toufaily C, Rassart E, Lafond J, Barbeau B. Syncytin-2 plays an important role in the fusion of human trophoblast cells. J Mol Biol 2009;392:301-318.
57. Vargas A, Toufaily C, LeBellego F, Rassart E, Lafond J, Barbeau B. Reduced expression of both syncytin 1 and syncytin 2 correlates with severity of preeclampsia. Reprod Sci 2011;18:1085-1091.
58. Whitehead CL, Walker SP, Ye L, Mendis S, Kaitu'u-Lino TJ, Lappas M, Tong S. Placental specific mRNA in the maternal circulation are globally dysregulated in pregnancies complicated by fetal growth restriction. J Clin Endocrinol Metab 2013;98:E429-E436.
59. Wice B, Menton D, Geuze H, Schwartz AL. Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 1990;186:306-316.
60. Yang M, LeiZM, RaoChV. The central role of human chorionic gonadotropin in the formation of human placental syncytium. Endocrinology 2003; 144:1108-1120.
61. Yu C, Shen K, Lin M, Chen P, Lin C, Chang GD, Chen H. GCMa regulates the syncytin-mediated trophoblastic fusion. J Biol Chem 2002;277:50062-8.
62. Zhao X, Monson C, Gao C, Gouon-Evans V, Matsumoto N, Sadler KC, Friedman SL. Klf6/copeb is required for hepatic outgrowth in zebrafish and for hepatocyte specification in mouse ES cells. Dev Biol 2010;344:79-93.