Decreased expression and activation of Stat3 in severe preeclampsia
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  • 作者:Zhan Zhang (1) (2) (3) (4)
    Xiaoqian Yang (1)
    Linlin Zhang (2) (3) (4)
    Zhenfeng Duan (5)
    Liting Jia (2) (3) (4)
    Peng Wang (2)
    Ying Shi (2)
    Ying Li (3) (4)
    Junjun Gao (2)

    1. Department of Obstetrics and Gynecology
    ; The Third Affiliated Hospital of Zhengzhou University ; 7 Kangfuqian Street ; Zhengzhou ; 450052 ; Henan Province ; China
    2. Department of Clinical Laboratory
    ; The Third Affiliated Hospital of Zhengzhou University ; Zhengzhou ; 450052 ; Henan Province ; China
    3. Henan Provincial Engineering Research Center for Perinatal Medicine
    ; The Third Affiliated Hospital of Zhengzhou University ; Zhengzhou ; 450052 ; Henan Province ; China
    4. Henan Translational Medicine Engineering Laboratory for Maternal and Children鈥檚 Health
    ; The Third Affiliated Hospital of Zhengzhou University ; Zhengzhou ; 450052 ; Henan Province ; China
    5. Center for Sarcoma and Connective Tissue Oncology
    ; Massachusetts General Hospital and Harvard Medical School ; Boston ; MA ; USA
  • 关键词:Severe preeclampsia ; Stat3 signal pathway ; Placenta ; Apoptosis ; Invasion
  • 刊名:Journal of Molecular Histology
  • 出版年:2015
  • 出版时间:April 2015
  • 年:2015
  • 卷:46
  • 期:2
  • 页码:205-219
  • 全文大小:18,180 KB
  • 参考文献:1. Benyo, DF, Smarason, A, Redman, CW, Sims, C, Conrad, KP (2001) Expression of inflammatory cytokines in placentas from women with preeclampsia. J Clin Endocrinol Metab 86: pp. 2505-2512
    2. Castellucci M, Kaufmann P (2006) Basic structure of the villous trees. In: Pathology of the human placenta. Springer, New York, pp 50鈥?20. doi:10.1007/0-387-26742-5_6
    3. Chen, Q, Stone, P, Ching, LM, Chamley, L (2009) A role for interleukin-6 in spreading endothelial cell activation after phagocytosis of necrotic trophoblastic material: implications for the pathogenesis of pre-eclampsia. J Pathol 217: pp. 122-130 CrossRef
    4. Corvinus, FM, Fitzgerald, JS, Friedrich, K, Markert, UR (2003) Evidence for a correlation between trophoblast invasiveness and STAT3 activity. Am J Reprod Immunol 50: pp. 316-321 CrossRef
    5. Cozzi, V, Garlanda, C, Nebuloni, M, Maina, V, Martinelli, A, Calabrese, S, Cetin, I (2012) PTX3 as a potential endothelial dysfunction biomarker for severity of preeclampsia and IUGR. Placenta 33: pp. 1039-1044 CrossRef
    6. Crocker, IP, Cooper, S, Ong, SC, Baker, PN (2003) Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am J Pathol 162: pp. 637-643 CrossRef
    7. Davison, JM (2004) New aspects in the pathophysiology of preeclampsia. J Am Soc Nephrol 15: pp. 2440-2448 CrossRef
    8. Demendi, C, Borzsonyi, B, Vegh, V, Nagy, ZB, Rigo, J, Pajor, A, Joo, JG (2012) Gene expression patterns of the Bcl-2 and Bax genes in preterm birth. Acta Obstet Gynecol Scand 91: pp. 1212-1217 CrossRef
    9. DiFederico, E, Genbacev, O, Fisher, SJ (1999) Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. Am J Pathol 155: pp. 293-301 CrossRef
    10. Fitzgerald, JS, Poehlmann, TG, Schleussner, E, Markert, UR (2008) Trophoblast invasion: the role of intracellular cytokine signalling via signal transducer and activator of transcription 3 (STAT3). Hum Reprod Update 14: pp. 335-344 CrossRef
    11. Garcia, MG (2007) High expression of survivin and down-regulation of Stat-3 characterize the feto-maternal interface in failing murine pregnancies during the implantation period. Placenta 28: pp. 650-657 CrossRef
    12. Gulati, S, Bhatnagar, S, Raghunandan, C, Bhattacharjee, J (2012) Interleukin-6 as a predictor of subclinical chorioamnionitis in preterm premature rupture of membranes. Am J Reprod Immunol 67: pp. 235-240 CrossRef
    13. Guo, Y, Xu, F, Lu, T, Duan, Z, Zhang, Z (2012) Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev 38: pp. 904-910 CrossRef
    14. Halperin, R, Peller, S, Rotschild, M, Bukovsky, I, Schneider, D (2000) Placental apoptosis in normal and abnormal pregnancies. Gynecol Obstet Investig 50: pp. 84-87 CrossRef
    15. Heazell, AE, Crocker, IP (2008) Live and let die鈥攔egulation of villous trophoblast apoptosis in normal and abnormal pregnancies. Placenta 29: pp. 772-783 CrossRef
    16. Heazell, AE, Buttle, HR, Baker, PN, Crocker, IP (2008) Altered expression of regulators of caspase activity within trophoblast of normal pregnancies and pregnancies complicated by preeclampsia. Reprod Sci 15: pp. 1034-1043 CrossRef
    17. Hirano, T, Ishihara, K, Hibi, M (2000) Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19: pp. 2548-2556 CrossRef
    18. Hu, C, Smith, SD, Pang, L, Sadovsky, Y, Nelson, DM (2006) Enhanced basal apoptosis in cultured term human cytotrophoblasts is associated with a higher expression and physical interaction of p53 and Bak. Placenta 27: pp. 978-983 CrossRef
    19. Huang, WL, Yeh, HH, Lin, CC, Lai, WW, Chang, JY, Chang, WT, Su, WC (2010) Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells. Mol Cancer 9: pp. 309 CrossRef
    20. Huppertz, B (2008) Placental origins of preeclampsia: challenging the current hypothesis. Hypertension 51: pp. 970-975 CrossRef
    21. Isaka, K (2003) Expression and activity of matrix metalloproteinase 2 and 9 in human trophoblasts. Placenta 24: pp. 53-64 CrossRef
    22. Ishihara, N, Matsuo, H, Murakoshi, H, Laoag-Fernandez, JB, Samoto, T, Maruo, T (2002) Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gynecol 186: pp. 158-166 CrossRef
    23. Jovanovic, M, Vicovac, L (2009) Interleukin-6 stimulates cell migration, invasion and integrin expression in HTR-8/SVneo cell line. Placenta 30: pp. 320-328 CrossRef
    24. Leung, DN, Smith, SC, To, KF, Sahota, DS, Baker, PN (2001) Increased placental apoptosis in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 184: pp. 1249-1250 CrossRef
    25. Li JJ et al (2008) Mcl-1 is regulated by IL-6 and mediates the survival activity of the cytokine in a model of late stage prostate carcinoma. In: Hormonal carcinogenesis V, vol 617. Advances in experimental medicine and biology. Springer, New York, pp 547鈥?55. doi:10.1007/978-0-387-69080-3_56
    26. Li, CF, Gou, WL, Li, XL, Wang, SL, Yang, T, Chen, Q (2012) Reduced expression of survivin, the inhibitor of apoptosis protein correlates with severity of preeclampsia. Placenta 33: pp. 47-51 CrossRef
    27. Liu, H, Ma, Y, Cole, SM, Zander, C, Chen, KH, Karras, J, Pope, RM (2003) Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival. Blood 102: pp. 344-352 CrossRef
    28. Lockwood, CJ (2008) Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells. Am J Pathol 172: pp. 1571-1579 CrossRef
    29. Lockwood, CJ (2008) Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells. Am J Pathol 172: pp. 1571-1579 CrossRef
    30. Lyall F (2011) The placenta in preeclampsia. In: The placenta. Wiley-Blackwell, pp 246鈥?52. doi:10.1002/9781444393927.ch32
    31. Muschol-Steinmetz, C, Friemel, A, Kreis, NN, Reinhard, J, Yuan, J, Louwen, F (2013) Function of survivin in trophoblastic cells of the placenta PloS one 8: pp. e73337
    32. Myatt, L (2002) Role of placenta in preeclampsia. Endocrine 19: pp. 103-111 CrossRef
    33. Omran, OM, Shokry, M, Ismail, H, Omar, G, Rezk, M (2011) Expression of matrix metalloproteinases 2 and 9 in human trophoblasts of normal and preeclamptic placentas. Int J Health Sci 5: pp. 21-23
    34. Onogi, A (2011) Hypoxia inhibits invasion of extravillous trophoblast cells through reduction of matrix metalloproteinase (MMP)-2 activation in the early first trimester of human pregnancy. Placenta 32: pp. 665-670 CrossRef
    35. Palei, AC, Sandrim, VC, Amaral, LM, Machado, JS, Cavalli, RC, Duarte, G, Tanus-Santos, JE (2012) Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy. Exp Mol Pathol 92: pp. 217-221 CrossRef
    36. Rampersad, R, Nelson, DM (2007) Trophoblast biology, responses to hypoxia and placental dysfunction in preeclampsia. Front Biosci J Virtual Library 12: pp. 2447-2456 CrossRef
    37. Robinson, CJ, Johnson, DD, Chang, EY, Armstrong, DM, Wang, W (2006) Evaluation of placenta growth factor and soluble Fms-like tyrosine kinase 1 receptor levels in mild and severe preeclampsia. Am J Obstet Gynecol 195: pp. 255-259 CrossRef
    38. Shiozaki, A, Kataoka, K, Fujimura, M, Yuki, H, Sakai, M, Saito, S (2003) Survivin inhibits apoptosis in cytotrophoblasts. Placenta 24: pp. 65-76 CrossRef
    39. Sibai, B, Dekker, G, Kupferminc, M (2005) Pre-eclampsia. Lancet 365: pp. 785-799 CrossRef
    40. Smith, SC, Baker, PN (1999) Placental apoptosis is increased in post-term pregnancies. Br J Obstet Gynaecol 106: pp. 861-862 CrossRef
    41. Soleymanlou, N (2007) Hypoxic switch in mitochondrial myeloid cell leukemia factor-1/Mtd apoptotic rheostat contributes to human trophoblast cell death in preeclampsia. Am J Pathol 171: pp. 496-506 CrossRef
    42. Staun-Ram, E, Goldman, S, Gabarin, D, Shalev, E (2004) Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion. Reprod Biol Endocrinol 2: pp. 59 CrossRef
    43. Takeda, K (1997) Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 94: pp. 3801-3804 CrossRef
    44. Tomas, SZ, Prusac, IK, Roje, D, Tadin, I (2011) Trophoblast apoptosis in placentas from pregnancies complicated by preeclampsia. Gynecol Obstet Investig 71: pp. 250-255 CrossRef
    45. Unek, G, Ozmen, A, Mendilcioglu, I, Simsek, M, Korgun, ET (2014) Immunohistochemical distribution of cell cycle proteins p27, p57, cyclin D3, PCNA and Ki67 in normal and diabetic human placentas. J Mol Histol 45: pp. 21-34 CrossRef
    46. Wang, L, Zhang, D, Yu, Y, Guan, H, Qiao, C, Shang, T (2013) RNA interference-mediated silencing of laminin receptor 1 (LR1) suppresses migration and invasion and down-regulates matrix metalloproteinase (MMP)-2 and MMP-9 in trophoblast cells: implication in the pathogenesis of preeclampsia. J Mol Histol 44: pp. 661-668 CrossRef
    47. Weber, M, Kuhn, C, Schulze, S, Jeschke, U, Markert, UR (2009) Immunohistochemical analysis of STAT3 and its phosphorylated forms in human placenta. J Reprod Immunol 81: pp. 172 CrossRef
    48. Weber, M (2012) Expression of signal transducer and activator of transcription 3 (STAT3) and its activated forms is negatively altered in trophoblast and decidual stroma cells derived from preeclampsia placentae. Histopathology 60: pp. 657-662 CrossRef
    49. Xie, TX, Wei, D, Liu, M, Gao, AC, Ali-Osman, F, Sawaya, R, Huang, S (2004) Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 23: pp. 3550-3560 CrossRef
    50. Xie, C, Yao, MZ, Liu, JB, Xiong, LK (2011) A meta-analysis of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in preeclampsia. Cytokine 56: pp. 550-559 CrossRef
    51. Xu, L, Lee, M, Jeyabalan, A, Roberts, JM (2014) The relationship of hypovitaminosis D and IL-6 in preeclampsia. Am J Obstet Gynecol 210: pp. e141-e147
    52. Zhang, H, Long, Q, Ling, L, Gao, A, Li, H, Lin, Q (2011) Elevated expression of KiSS-1 in placenta of preeclampsia and its effect on trophoblast. Reprod Biol 11: pp. 99-115 CrossRef
    53. Zhang, X (2011) Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model. Eur J Pharmacol 667: pp. 202-207 CrossRef
    54. Zhang Z, Zhang L, Jia L, Wang P, Gao Y (2013a) Association of Wnt2 and sFRP4 expression in the third trimester placenta in women with severe preeclampsia. Reprod Sci (Thousand Oaks, Calif) 20:981鈥?89. doi:10.1177/1933719112472740
    55. Zhang Z, Zhang L, Jia L, Wang P, Gao Y (2013b) Association of Wnt2 and sFRP4 expression in the third trimester placenta in women with severe preeclampsia. Reprod Sci. doi:10.1177/1933719112472740
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Cell Biology
    Biomedicine
    Developmental Biology
  • 出版者:Springer Netherlands
  • ISSN:1567-2387
文摘
Severe preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Signal transducer and activator of transcription 3 (Stat3) signal pathway can modulate various fundamental cellular processes. However, whether Stat3 plays a role in the pathogenesis of severe PE is unknown. Therefore, in this study, the expression levels of Stat3 pathway-related genes and proteins, Stat3, pStat3, IL-6, Mcl-1L, Bcl-xL, survivin, MMP-2, and MMP-9, were evaluated by immunohistochemistry (IHC), Western blot analysis and real-time PCR in the severe preeclamptic placentas. Our results showed that Stat3 and pStat3 immunoreactivity were localized in both extravillous cytotrophoblast cells and villous trophoblast cells in the placentas. As compared with normotensive pregnancies, significantly decreased expressions of Stat3 and pStat3 proteins were observed in extravillous cytotrophoblast cells, villous trophoblast cells and entire placentas in patients with severe PE. The expression levels of Stat3, IL-6, survivin and MMP-2 mRNA were significantly decreased in severe preeclamptic placentas, while Mcl-1L, Bcl-xL and MMP-9 mRNA levels were unchanged. IHC results further confirmed that there was a significant decrease of IL-6, survivin and MMP-2 proteins expression in the severe preeclamptic placentas compared with the normal specimens. These findings suggested that decreased expression and activation of the Stat3 may be caused by decreased expression of a Stat3 upstream gene, such as IL-6. Decreased Stat3 expression and activation may play an important role in the pathogenesis of PE through regulation of the transcription of the Stat3 targeted genes survivin and MMP-2 to modulate apoptosis and invasion of placental trophoblastic cells.

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