Vol 90, No 1 (2019)
Research paper
Published online: 2019-01-31

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Decreased Filamin b expression regulates trophoblastic cells invasion through ERK/MMP-9 pathway in pre-eclampsia

Jufeng Wei1, Yufen Fu2, Xiaoling Mao3, Yuhui Jing3, Jiangbo Guo3, Yuanhua Ye4
Pubmed: 30756369
Ginekol Pol 2019;90(1):39-45.

Abstract

Objectives: The purpose of this study was to investigate the expression of Filamin b in the placental placenta of patients with early or late onset pre-eclampsia (PE) and its potential effects on the pathophysiology of the disease.

Methods and methods: Immunohistochemistry staining, western blot assays and real time PCR were used to detect the expression level of FLN-b. The expression levels of MMP-2, MMP-9 and ERK1/2 proteins from control and FLN-b-silenced JEG-3 cells were also detected by western blot and JEG-3 cell invasion.

Results: Compared with normal term pregnancies placentas, the FLN-b expression was significantly lower than that of women with PE, its level in late-onset PE is lower than in early-onset PE. In FLN-b-silenced JEG-3 cells, the protein levels of MMP-2, MMP-9 and phosphorylated ERK1/2 decreased markedly and the number of cells penetrating through the transwell chamber membrane is also greatly reduced.

Conclusions: Down-regulation of FLN-b inhibits the ERK/MMP-2 and MMP-9 pathways, leading to trophoblastic invasion disorders in the PE placenta.  

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References

  1. Cornelius DC. Preeclampsia: From Inflammation to Immunoregulation. Clin Med Insights Blood Disord. 2018; 11: 1179545X17752325.
  2. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005; 308(5728): 1592–1594.
  3. Maynard SE, Venkatesha S, Thadhani R, et al. Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia. Pediatr Res. 2005; 57(5 Pt 2): 1R–7R.
  4. Stossel TP, Condeelis J, Cooley L, et al. Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol. 2001; 2(2): 138–145.
  5. Zhou X, Borén J, Akyürek LM. Filamins in cardiovascular development. Trends Cardiovasc Med. 2007; 17(7): 222–229.
  6. Zhou AX, Hartwig JH, Akyürek LM. Filamins in cell signaling, transcription and organ development. Trends Cell Biol. 2010; 20(2): 113–123.
  7. Guedj N, Zhan Q, Perigny M, et al. Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas. J Hepatol. 2009; 51(1): 93–101.
  8. Li C, Yu S, Nakamura F, et al. Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer. J Clin Invest. 2009; 119(9): 2725–2736.
  9. Bedolla RG, Wang Yu, Asuncion A, et al. Nuclear versus cytoplasmic localization of filamin A in prostate cancer: immunohistochemical correlation with metastases. Clin Cancer Res. 2009; 15(3): 788–796.
  10. Alper O, Stetler-Stevenson WG, Harris LN, et al. Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma. Cancer Sci. 2009; 100(9): 1748–1756.
  11. Bandaru S, Zhou AX, Rouhi P, et al. Targeting filamin B induces tumor growth and metastasis via enhanced activity of matrix metalloproteinase-9 and secretion of VEGF-A. Oncogenesis. 2014; 3: e119.
  12. Iguchi Y, Ishihara S, Uchida Y, et al. Filamin B Enhances the Invasiveness of Cancer Cells into 3D Collagen Matrices. Cell Struct Funct. 2015; 40(2): 61–67.
  13. Thompson TG, Chan YM, Hack AA, et al. Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein. J Cell Biol. 2000; 148(1): 115–126.
  14. Kalhori V, Törnquist K. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells. Mol Cell Endocrinol. 2015; 404: 113–122.
  15. McCain J. The MAPK (ERK) Pathway: Investigational Combinations for the Treatment Of BRAF-Mutated Metastatic Melanoma. P T. 2013; 38(2): 96–108.
  16. Davidson B, Givant-Horwitz V, Lazarovici P, et al. Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases (MAPK): co-expression in metastatic serous ovarian carcinoma. Clin Exp Metastasis. 2003; 20(7): 621–631.
  17. Ferretti C, Bruni L, Dangles-Marie V, et al. Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum Reprod Update. 2007; 13(2): 121–141.
  18. Cohen M, Bischof P. Factors regulating trophoblast invasion. Gynecol Obstet Invest. 2007; 64(3): 126–130.
  19. Husslein H, Haider S, Meinhardt G, et al. Expression, regulation and functional characterization of matrix metalloproteinase-3 of human trophoblast. Placenta. 2009; 30(3): 284–291.
  20. Xu B, Nakhla S, Makris A, et al. TNF-α inhibits trophoblast integration into endothelial cellular networks. Placenta. 2011; 32(3): 241–246.
  21. Saito S, Nakashima A. A review of the mechanism for poor placentation in early-onset preeclampsia: the role of autophagy in trophoblast invasion and vascular remodeling. J Reprod Immunol. 2014; 101-102: 80–88.
  22. Zou J, Xu Li, Ju Y, et al. Cholesterol depletion induces ANTXR2-dependent activation of MMP-2 via ERK1/2 phosphorylation in neuroglioma U251 cell. Biochem Biophys Res Commun. 2014; 452(1): 186–190.
  23. Zhou X, Tian F, Sandzén J, et al. Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development. Proc Natl Acad Sci U S A. 2007; 104(10): 3919–3924.
  24. Bandaru S, Zhou AX, Rouhi P, et al. Targeting filamin B induces tumor growth and metastasis via enhanced activity of matrix metalloproteinase-9 and secretion of VEGF-A. Oncogenesis. 2014; 3: e119.
  25. Jia RZ, Rui C, Li JY, et al. CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression. Placenta. 2014; 35(7): 450–454.