The Relationship Between MicroRNAs And Congenital Kidney Anomalies

Objective: The purpose of this study was to identify diagnostic microRNAs (miRNAs) associated with congenital kidneyanomalies.Methods: Twenty-five healthy pregnant women who were found to have fetal kidney anomaly in the second trimester oftheir pregnancy at Department of Perinatology, were included in the study. Serum samples were taken from the pregnantwomen at the moment of diagnosis in the antenatal 20th gestational week, whereas serum samples were taken from thecord blood of babies during birth. There were 11 multicystic dysplastic kidney patients, 6 autosomal recessive polycystickidney patients, and 8 unilateral hypoplastic kidney patients. Expression of specific miRNAs was monitored using specificprimer assays in Real-Time PCR. The expression of the following miRNAs was quantified: miR-17, miR-192, miR-194,miR-204, miR-215, and miR-216.Results: mir-17 expression was significantly lower in children with congenital kidney anomalies than in the controlgroup. ROC curve analysis showed that the area under the curve was 0.700 for miR-17 in the prediction of congenitalkidney anomalies.Conclusions: In children with congenital kidney anomalies, miR-17 expression was significantly different than in thecontrol group. Thus, this miRNA may be used in the antenatal early detection of these congenital kidney anomalies.

MikroRNA’lar ve Doğuştan Böbrek Anomalileri Arasındaki İlişki

Amaç: Bu çalışmanın amacı, doğuştan böbrek anomalileri ile ilişkili tanısal mikroRNA’ların tespit edilmesidir. Yöntemler: Perinatoloji bölümünde gebeliklerinin ikinci trimesterinde fetüste böbrek anomalisine sahip olan 25 sağlıklı gebe çalışmaya dahil edildi. Gebeliğin 20. Haftasında tanı anında gebelerden, doğum anında bebeklerin kord kanından serum örnekleri alındı. 11 hastada multikistik displastik böbrek, 6 hastada otozomal resesif polikistik böbrek ve 8 hastada tek taraflı hipoplastik böbrek vardı. Spesifik miRNA'ların ekspresyonu, Real-Time PCR'da spesifik primer analizler kullanılarak izlendi. Aşağıdaki miRNA'ların ekspresyonu ölçüldü: miR-17, miR-192, miR-194, miR-204, miR-215 ve miR216. Bulgular: mir-17 ekspresyonu doğuştan böbrek anomalisi olan çocuklarda kontrol grubuna göre önemli derecede düşüktü. ROC eğrisi analizi, doğuştan böbrek anomalilerinin öngörülmesinde eğri altındaki alanın miR-17 için 0.700 olduğunu göstermiştir. Sonuç: Doğuştan böbrek anomalisi olan çocuklarda, miR-17 ekspresyonu kontrol grubundan önemli derecede farklıydı. Bu nedenle, bu miRNA, doğuştan böbrek anomalilerinin antenatal erken tespitinde kullanılabilir.

___

1. Vivante A, Kohl S, Hwang DY, Dworschak GC, Hildebrandt F. Single-genecauses of congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Pediatr Nephrol. 2014; 29: 695-704.

2. Ho J, Kreidberg JA. MicroRNAs in renal development. Pediatr Nephrol. 2013; 28: 219- 25.

3. Dias T, Sairam S, Kumarasiri S. Ultrasound diagnosis of fetal renal abnormalities. Best Pract Res Clin Obstet Gynaecol. 2014; 28: 403-15.

4. van de Hoek G, Nicolaou N, Giles RH, Knoers NV, Renkema KY, Bongers EM. Functional models for congenital anomalies of the kidney and urinary tract. Nephron. 2015; 129: 62-7.

5. dos Santos Junior AC, de Miranda DM, Simões e Silva AC. Congenital anomalies of the kidney and urinary tract: an embryogenetic review. Birth Defects Res C Embryo Today. 2014; 102: 374-81.

6. Caruana G, Bertram JF. Congenital anomalies of the kidney and urinary tract genetics in mice and men. Nephrology (Carlton). 2015; 20: 309- 11.

7. Baldassarre A, Felli C, Prantera G, Masotti A. Circulating microRNAs and Bioinformatics Tools to Discover Novel Diagnostic Biomarkers of Pediatric Diseases. Genes (Basel). 2017; 8: 234.

8. Makarova JA, Shkurnikov MU, Turchinovich AA, Tonevitsky AG, Grigoriev AI. Circulating microRNAs. Biochemistry (Mosc). 2015; 80: 1117-26.

9. Ivey KN, Srivastava D. microRNAs as Developmental Regulators. Cold Spring Harb Perspect Biol. 2015; 7: a008144.

10. Van der Hauwaert C, Savary G, Hennino MF, Pottier N, Glowacki F, Cauffiez C. MicroRNAs in kidney fibrosis. Nephrol Ther. 2015; 11: 474-82.

11. Kito N, Endo K, Ikesue M, Weng H, Iwai N. miRNA Profiles of Tubular Cells: Diagnosis of Kidney Injury. Biomed Res Int. 2015; 2015: 465479.

12. Akkina S, Becker BN. MicroRNAs in kidney function and disease. Transl Res. 2011; 157: 236-40.

13. Badal SS, Danesh FR. MicroRNAs and their applications in kidney diseases. Pediatr Nephrol. 2015; 30: 727-40.

14. Trionfini P, Benigni A, Remuzzi G. MicroRNAs in kidney physiology and disease. Nat Rev Nephrol. 2015; 11: 23-33.

15. Bhatt K, Kato M, Natarajan R. Mini-review: emerging roles of microRNAs in the pathophysiology of renal diseases. Am J Physiol Renal Physiol. 2016; 310: 109-18.

16. Ho J, Pandey P, Schatton T, et al. The proapoptotic protein Bim is a MicroRNA target in kidney progenitors. J Am Soc Nephrol. 2011; 22: 1053–63.

17. Nagalakshmi VK, Ren Q, Pugh MM, Valerius MT, McMahon AP, Yu J. Dicer regulates the development of nephrogenic and ureteric compartments in the mammalian kidney. Kidney Int. 2011; 79: 317-30.

18. Zhao H, Ma SX, Shang YQ, Zhang HQ, Su W. micro RNAs in chronic kidney disease. Clin Chim Acta. 2019; 491: 59-65.

19. Hartung EA, Guay-Woodford LM. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects. Pediatrics. 2014; 134: 833- 45.

20. Pandey P, Brors B, Srivastava PK, et al. Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease. BMC Genomics. 2008; 9: 624.

21. Sun H, Li QW, Lv XY, et al. MicroRNA-17 posttranscriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation. MolBiol Rep. 2010; 37: 2951–8.

22. Lee SO, Masyuk T, Splinter P, et al. MicroRNA15a modulates expression of the cellcycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Invest. 2008; 118: 3714–24.

23. Ho J, Pandey P, Schatton T, et al. The proapoptotic protein Bim is a MicroRNA target in kidney progenitors. J Am Soc Nephrol. 2011; 22: 1053–63.

24. Zhu S, Cao L, Zhu J, et al. Identification of maternal serum microRNAs as novel noninvasive biomarkers for prenatal detection of fetal congenital heart defects. Clin Chim Acta. 2013; 424: 66-72.

25. Song Y, Higgins H, Guo J, et al. Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children. J Transl Med. 2018; 2: 42.

26. Wojciechowska A, Braniewska A, KozarKamińska K. MicroRNA in cardiovascular biology and disease. Adv Clin Exp Med. 2017; 26: 865-74.

27. Weber DG, Casjens S, Rozynek P, et al. Assessment of mRNA and microRNA Stabilization in Peripheral Human Blood for Multicenter Studies and Biobanks. Biomark Insights. 2010; 5: 95-102.
Dicle Tıp Dergisi-Cover
  • ISSN: 1300-2945
  • Yayın Aralığı: 4
  • Başlangıç: 1963
  • Yayıncı: Cahfer GÜLOĞLU
Sayıdaki Diğer Makaleler

MikroRNA’lar ve Doğuştan Böbrek Anomalileri Arasındaki İlişki

Zübeyde GÜNDÜZ, Ruhan DÜŞÜNSEL, Sibel YEL, Kenan YILMAZ, Mehmet Serdar KUTUK, İsmail DURSUN

Malign Plevral Mezotelyomada Metabolik PET Parametrelerinin Sağkalım Üzerine Etkisi

Şahin LAÇİN, Abdurrahman IŞIKDOĞAN, Nadiye AKDENİZ, Mehmet KÜÇÜKÖNER, Muhammet Ali KAPLAN, Zuhat URAKÇI, Oğur KARHAN, Halis YERLİKAYA, Halil KÖMEK

The Relationship Between Acute Renal Failure After Transcatheter Aortic Valve Replacement And Preprocedural Neutrophil To Lymphocyte Ratio

Nizamettin Selçuk YELGEÇ, Mehmet Baran KARATAŞ, Can Yücel KARABAY, Yiğit ÇANGA, Ali Nazmi ÇALIK, Barış ŞİMŞEK, Özge GÜZELBURÇ, Ayşe MERE

Kliniğimizde Cerrahi Olarak Tedavi Edilen Göz Kapağı Tümörlerinin Histopatolojik Bulguları

Dilek UZLU, Nurettin AKYOL, Mustafa Emre ERCİN, Adem TÜRK, Halil İbrahim İMAMOĞLU

Non-Valvuler Atriyal Fibrilasyonu Olan Hastalarda Kanama Risk Sınıflandırılmasında Platelet-Lenfosit Oranının Yeni Kullanımları: Pilot Çalışma

Kahraman COŞANSU, Cagın Mustafa UREYEN, Harun KILIÇ, Bilgehan KARADAĞ, Ayca TURER CABBAR, Huseyin GUNDUZ, Rmazan AKDEMİR

Cerrahi Olarak Tedavi Edilen Distal Radius Kırıklarının Klinik Profili

Tolgahan KURU, Onur YILMAZ

Analysis of Patients Undergoing Peripartum Hysterectomy for Obstetric Causes According to Delivery Methods: 13-Year Experience of a Tertiary Center

Nurullah PEKER, Gökçe TURAN, Edip AYDIN, Mustafa YAVUZ, Serhat EGE, Muhammet Hanifi BADEMKIRAN, Talip KARACOR, Talip GÜL

Pulmoner Arteriyal Hipertansiyon Hastalarında Serum D vitamini Düzeyleri

Ümit Yaşar SİNAN, İsmail Polat CANBOLAT, Ayşem KAYA

Yaş Tip Senil Maküla Dejeneresansı Olan Hastalarda İntravitreal Enjeksiyonun Okülokardiak Refleks Üzerine Etkisi

Mine KARAHAN, Seyfettin ERDEM, Sedat AVA, Mehmet Emin DURSUN, Zülküf KARAHAN, Atılım Armağan DEMİRTAŞ, Uğur KEKLİKÇİ

Value Of Cephalometric And Volumetric Measurements Performed By Multi-Level Three-Dimensional Computed Tomography In Patients With Obstructive Sleep Apnea Syndrome

Feride Fatma GÖRGÜLÜ, Sıdıka Deniz YALIM