nach oben

Erschienen in:

27.02.2020 | Maternal-Fetal Medicine

H19 regulates angiogenic capacity of extravillous trophoblasts by H19/miR-106a-5p/VEGFA axis

verfasst von: Hong Zeng, Dongmei He, Hebin Xie, Yuhao Zhao, Zhaoqun Peng, Huan Deng, Jinyue Hu, Binyuan Jiang, Nenghui Liu

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To investigate the role and underlying mechanism of H19 in regulating angiogenic capacity of extravillous trophoblasts.

Methods

Gain and loss of function experiments were performed using a human first-trimester extravillous trophoblast (EVT) cell line, HTR-8/SVneo cells. H19 was overexpressed or knocked down in HTR-8 cells by transfecting plasmid harboring whole-length H19 sequence (pH19) or siRNA specially targeting H19, respectively (siH19). Cell migration and tube-formation assay were assessed in the indicated groups. Gene expression was detected by RT-qPCR, Western blot, and ELISA assay.

Results

Overexpression of H19 in EVT cells increased cell migration and tube formation, while downregulation of H19 in EVT cells decreased cell migration and tube formation. Furthermore, we found that H19 played its role by VEGFA. In addition, we demonstrated the H19/miR-106a-5p/VEGFA regulatory axis in EVT. Experiments of the clinical specimen showed that H19 was very abundantly expressed in human first-trimester trophoblasts, and we found that the expression of H19 and VEGFA were significantly downregulated in the villous tissues from idiopathic recurrent miscarriage (RM) patients; moreover, the expression of H19 and VEGFA was positively correlated.

Conclusion

H19/miR-106a-5p/VEGFA axis plays a role in regulating the angiogenic capacity of EVT, which might contribute to idiopathic RM.

He D, Zeng H, Chen J et al (2019) H19 regulates trophoblastic spheroid adhesion by competitively binding to let-7. Reprod 157(5):423–430CrossRef

Zuckerwise L, Li J, Lu L et al (2016) H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TbetaR3 in placentae with fetal growth restriction. Oncotarget 7(25):38398–38407CrossRef

Torry DS, Leavenworth J, Chang M et al (2007) Angiogenesis in implantation. J Assist Reprod Genet 24(7):303–315CrossRef

Wulff C, Weigand M, Kreienberg R et al (2003) Angiogenesis during primate placentation in health and disease. Reproduction 126(5):569–577CrossRef

Bischof P, Irminger-Finger I (2005) The human cytotrophoblastic cell, a mononuclear chameleon. Int J Biochem Cell Biol 37(1):1–16CrossRef

Ishii T, Miyazawa M, Takanashi Y et al (2014) Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion. Redox Biol 2:679–685CrossRef

Banerjee P, Ghosh S, Dutta M et al (2013) Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage. PLoS ONE 8(11):e80940CrossRef

Zhu Y, Lu H, Huo Z et al (2016) MicroRNA-16 inhibits feto-maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor. Sci Rep 6:35536CrossRef

Klauber N, Rohan RM, Flynn E et al (1997) Critical components of the female reproductive pathway are suppressed by the angiogenesis inhibitor AGM-1470. Nat Med 3(4):443–446CrossRef

10.

Meegdes BH, Ingenhoes R, Peeters LL et al (1988) Early pregnancy wastage: relationship between chorionic vascularization and embryonic development. Fertil Steril 49(2):216–220CrossRef

11.

Zeng H, Fan X, Liu N (2017) Expression of H19 imprinted gene in patients with repeated implantation failure during the window of implantation. Arch Gynecol Obstet 296(4):835–839CrossRef

12.

Poirier F, Chan CT, Timmons PM et al (1991) The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development 113(4):1105–1114PubMed

13.

Xu J, Xia Y, Zhang H et al (2018) Overexpression of long non-coding RNA H19 promotes invasion and autophagy via the PI3K/AKT/mTOR pathways in trophoblast cells. Biomed Pharmacother 101:691–697CrossRef

14.

Jauniaux E, Poston L, Burton GJ (2006) Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Update 12(6):747–755CrossRef

15.

Voellenkle C, Garcia-Manteiga JM, Pedrotti S et al (2016) Implication of long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing. Sci Rep 6(1):24141CrossRef

16.

Hou J, Wang L, Wu Q et al (2018) Long noncoding RNA H19 upregulates vascular endothelial growth factor A to enhance mesenchymal stem cells survival and angiogenic capacity by inhibiting miR-199a-5p. Stem Cell Res Ther 9(1):109CrossRef

17.

Zhang C, Li Q, Ren N et al (2015) Placental miR-106a~363 cluster is dysregulated in preeclamptic placenta. Placenta 36(2):250–252CrossRef

18.

Premlata K, Yanmin L, Carmen T et al (2013) The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a~363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation. Mol Cell Biol 33(9):1782–1796CrossRef

19.

Fang Y, Yu S, Ma Y et al (2013) Association of Dll4/notch and HIF-1a-VEGF signaling in the angiogenesis of missed abortion. PLoS ONE 8(8):e70667CrossRef

20.

Meher A, Sundrani D, Joshi S (2015) Maternal nutrition influences angiogenesis in the placenta through peroxisome proliferator activated receptors: a novel hypothesis. Mol Reprod Dev 82(10):726–734CrossRef

21.

De Falco S (2012) The discovery of placenta growth factor and its biological activity. Exp Mol Med 44(1):1–9CrossRef

22.

Hiratsuka S, Kataoka Y, Nakao K et al (2005) Vascular endothelial growth factor A (VEGF-A) is involved in guidance of VEGF receptor-positive cells to the anterior portion of early embryos. Mol Cell Biol 25(1):355–363CrossRef

23.

Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581–611CrossRef

24.

Amirchaghmaghi E, Rezaei A, Moini A et al (2015) Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J 16(4):538–545PubMedPubMedCentral

25.

Kutluer G, Cicek NM, Moraloglu O et al (2012) Low VEGF expression in conceptus material and maternal serum AFP and beta-hCG levels as indicators of defective angiogenesis in first-trimester miscarriages. J Turk Ger Gynecol Assoc 13(2):111–117PubMedPubMedCentral

26.

Bagheri A, Kumar P, Kamath A et al (2017) Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage. Bratisl Lek Listy 118(5):258–264PubMed

27.

Plaisier M, Dennert I, Rost E et al (2009) Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum Reprod 24(1):185–197CrossRef

28.

Vuorela P, Carpen O, Tulppala M et al (2000) VEGF, its receptors and the tie receptors in recurrent miscarriage. Mol Hum Reprod 6(3):276–282CrossRef

29.

Almawi WY, Saldanha FL, Mahmood NA et al (2013) Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Hum Reprod 28(10):2628–2635CrossRef

Titel: H19 regulates angiogenic capacity of extravillous trophoblasts by H19/miR-106a-5p/VEGFA axis
verfasst von: Hong Zeng
Dongmei He
Hebin Xie
Yuhao Zhao
Zhaoqun Peng
Huan Deng
Jinyue Hu
Binyuan Jiang
Nenghui Liu
Publikationsdatum: 27.02.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 3/2020
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-020-05469-7

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

H19 regulates angiogenic capacity of extravillous trophoblasts by H19/miR-106a-5p/VEGFA axis