Prokinetisin 1 preeklampsi belirteci olarak kullanılabilir mi?

Öz

Prokinetisin 1 preeklampsi belirteci olarak kullanılabilir mi? Amaç: Prokinetisinler, gastrointestinal sistemde görev aldığı saptanan bir grup peptidden oluşur ve 3 alt gruba ayrılır. Anjiogenezde, hematopoezde ve üremede önemli rolleri olduğu saptanmıştır. Anjiogenezde vasküler endotelyal büyüme faktörüne (VEGF) benzer rol aldığından dolayı EG-VEGF (endokrin gland kaynaklı vasküler endotelyal büyüme faktörü) olarak da adlandırılır. Bağışıklık sistemiyle de ilişkili olduğu gösterilen prokinetisinlerin kadın genitoüriner sistemini en çok etkileyen alt grubu prokinetisin 1’dir (PROK1). PROK1 sinsityotrofoblastlardan salınmakta olup plasentanın büyüme ve matürasyonu için hayati öneme sahiptir. PROK1, extravillöz trofoblastik hücre göçünü ilk trimesterde engeller. Hipoksi, PROK1’in ekspresyonunu uyararak preeklamptik gebelerde serum PROK1 düzeyini arttırır. Bu çalışma ile PROK 1 preeklampsi (PE) öngörüsünde bir belirteç olarak kullanabilir mi sorusuna cevap aramaktayız. Gereçler ve Yöntem: Çalışmaya Ümraniye Araştırma ve Eğitim Hastanesi Kadın Hastalıkları ve Doğum Kliniği'nde Ekim 2016-Eylül 2017 tarihleri arasında başvuran 84 gebe dahil edildi. PE tanısı alan 43 gebe vaka grubuna, 41 sağlıklı gebe kontrol grubuna dahil edildi. PE grubu; hafif PE (n=27) ve şiddetli PE (n=16) olmak üzere iki alt gruba ayrıldı. Bulgular: Gruplar arasında anne yaşı (yıl) ve başvuru sırasındaki gebelik yaşı açısından anlamlı bir fark saptanmadı. Doğum haftası, PE grubunda kontrol grubuna göre anlamlı olarak daha kısaydı (38.8 ± 1.43'e karşı 35.93 ± 3.5; p<0.001). PE grubunda fetal ağırlık, kontrol grubuna göre önemli ölçüde daha düşüktü (3262.8±403.9'a karşı 2806.8±886.06; p=0.003). PROK1 düzeyleri çalışma grupları arasında benzerdi (115,66±22,41 vs 115,57±26,27; p=0,91). Hafif PE grupta PROK1 düzeyi, şiddetli PE ve kontrol gruplarına göre daha düşüktü, fakat bu sapma istatistiksel olarak anlamlı bulunmadı. Sonuç: Çalışmamızda PROK1’in, PE belirteci olarak kullanılabileceğini gösteren istatistiksel anlamlı bir sonuca ulaşılamaması göstermektedir ki, bu belirtecin preeklampsideki rolünü belirlemek için daha büyük ölçekli ve daha ileri çalışmalara ihtiyaç vardır. Anahtar kelimeler: preeklampsi, prokinetisin 1, belirteç

Anahtar Kelimeler

• preeklampsi
• prokinetisin 1
• belirteç

Can prokineticin 1 be used as a biomarker in preeclampsia?

Öz

Abstract Can prokineticin 1 be used as a biomarker in preeclampsia? Aim: Prokineticins are a group of peptides which play important roles in angiogenesis, hematopoiesis and reproduction. Prokineticin 1 (PROK1) is reported to be the major subgroup affecting the female reproductive development. PROK1 is secreted from the syncytiotrophoblasts and it prevents extravillous trophoblastic cell migration in the first trimester which predispose to the abnormal placentation and preeclampsia (PE). Hypoxia provokes the expression of PROK1 therefore its serum levels increase in pregnants with PE. The aim of the present study was to reveal the value of PROK1 as a marker of PE. Materials and Method: A total of 84 pregnant women were admitted to the study, and 43 of them were diagnosed with preeclampsia. 41 healthy pregnant women were included in the control group. The preeclampsia group was divided into two subgroups as mild PE (n=27) and severe PE (n=16). About 10 ml of venous blood was collected from each participant and dispensed into lithium heparin, and serum was obtained, which were stored at – 80 c until analyzed. Serum PROK1 measurements were performed by using an enzyme-linked immunosorbent assay (ELİSA). All tests were two-tailed, and p<0.05 was considered to be statistically significant. Results: In our study we did not find any significant difference in PROK1 levels of the two groups. (115.66±22.41 vs115.57±26.27; p=0.91). Groups showed no significant differences in maternal age (years) and gestational age at admission. The preeclamptic group was separated into the two groups as mild PE (n=27) and severe PE (n=16) (Table 3). The prokineticin 1 level was lower in the mild preeclamptic group than the severe and control groups and this declination did not reach statistical significance. Conclusion: PROK1 is thought to play role in the etiology of PE regarding the fact that this peptide affects the trophoblast invasion and placental angiogenesis. Although our present study did not reach a result indicating PROK1 as a predictor of PE, larger scaled studies are needed to clarify the role of this factor in PE. Key words: preeclampsia, prokineticin 1, predictor

Anahtar Kelimeler

• preeclampsia
• prokinetcin 1
• predictor

Kaynakça

1. [1] Li M, et al. Identification of two prokineticin cDNAs: recombinant pro- teins potently contract gastrointestinal smooth muscle. Mol Pharmacol 2001;59:692–8.
2. [2] LeCouter J, Ferrara N. EG-VEGF and the concept of tissue-specific angio- genic growth factors. Semin Cell Dev Biol 2002;13:3–8.
3. [3] LeCouter J, et al. Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization. Proc Natl Acad Sci U S A 2004;101:16813–8.
4. [4] Ngan ES, et al. Prokineticin-1 (Prok-1) works coordinately with glial cell line-derived neurotrophic factor (GDNF) to mediate proliferation and differentiation of enteric neural crest cells. Biochim Biophys Acta 2008;1783:467–78.
5. [5] Brouillet S, et al. EG-VEGF: a key endocrine factor in placental develop- ment. Trends Endocrinol Metab 2012;23:501–8.
6. [6] Hoffmann P, Feige JJ, Alfaidy N. Placental expression of EG-VEGF and its receptors PKR1 (prokineticin receptor-1) and PKR2 throughout mouse gestation. Placenta 2007;28:1049–58.
7. [7] LeCouter J, et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 2001;412:877–84.
8. [8] Brouillet S, et al. Molecular characterization of EG-VEGF-mediated angiogenesis: differential effects on microvascular and macrovascular endothelial cells. Mol Biol Cell 2010;21:2832–43.

9. [9] Hoffmann P, et al. Role of EG-VEGF in human placentation: physiological and pathological implications. J Cell Mol Med 2009;13:2224–35.
10. [10] Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005;365:785–99.
11. [11] Brouillet S, et al. Revisiting the role of hCG: new regulation of the angiogenic factor EG-VEGF and its receptors. Cell Mol Life Sci 2012;69:1537–50.
12. [12] Hoffmann P, Feige JJ, Alfaidy N. Expression and oxygen regulation of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy. Endocrinology 2006;147:1675–84.
13. [13] Sergent F, Hoffmann P, Brouillet S, Garnier V, Salomon A, Murthi P, Ben- harouga M, Feige JJ, Alfaidy N. Sustained EG-VEGF levels beyond the first-trimester of pregnancy display phenotypic and functional changes associated with the pathogenesis of pregnancy-induced hypertension. Hypertension 2016;68.
14. [14] Petrik JJ, et al. Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine. Endocrine 2009;36:281–90.
15. [15] Ajonuma LC, et al. EG-VEGF concentrations may predict OHSS. Fertil Steril 2011;95:e37–8.
16. [16] Karaer A, et al. Prokineticin 1 and leukemia inhibitory factormRNAexpres- sion in the endometrium of women with idiopathic recurrent pregnancy loss. Fertil Steril 2014;102:1091e1–5e1.
17. [17] Salker M, et al. Natural selection of human embryos: impaired decidual- ization of endometrium disables embryo–maternal interactions and causes recurrent pregnancy loss. PLoS One 2010;5:pe10287.
18. [18] T. Goi, M. Fujioka, Y. Satoh et al., “Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line sw620 transfected with endocrine glands-derived-vascular endothelial growth factor, as a new angiogenic factor,” Cancer Research, vol. 64, no. 6, pp. 1906–1910, 2004.
19. [19] S. Bălu, L. Pirtea, P. Gaje, A. M. Cîmpean, and M. Raica, “The immunohistochemical expression of endocrine glandderived- VEGF (EG-VEGF) as a prognostic marker in ovarian cancer,” Romanian Journal of Morphology and Embryology, vol. 53, no. 3, pp. 479–483, 2012.
20. [20] C. Inan, F.G. Varol, S.G. Erzincan, I. Uzun, H. Sutcu, N.C. Sayin, Use of prokineticin-1 (PROK1), pregnancy associated plasma protein A (PAPP-A) and PROK1/PAPP-A ratio to predict adverse pregnancy outcomes in the first trimester: a prospective study, J. Matern. Fetal Med. (2017), https://doi.org/10.1080/14767058.2017.1351536. Volume 31, 2018 -Issue 20 Pages 2685-2692.