ABSTRACT
Nephrotic syndrome (NS) in children has some mysterious prognosis in the perspective of its therapeutic response. This study aims to determine the role of miR-21 in β-2 microglobulin (B2M) expression among SRNS children. The open-prospective cohort study was conducted at Hasan Sadikin General Hospital, Indonesia. A total of 24 children (age 1–18 years) with NS were enrolled in this study. Meanwhile, blood samples were collected prior to any treatment. The whole blood samples were collected from 12 SRNS and control. Moreover, RNA isolation was carried out with blood plasma samples stored in a cooler at -800C, while miR-21 expression was measured using qRT-PCR. The difference between miRNAs expression analyzed with Livak and the correlation between B2M and miR-21 expression were analyzed using Spearman correlation analysis. Based on the results, there were notable upregulation of miR-21 in SRNS compared to SSNS 2-ΔΔCt > 1. However, no correlation was observed between B2M expression with the upregulation of miR-21 ( -1 < rs < 1, p > 0.05). The miR-21 is upregulated in children with SRNS. This indicates that the expression level of this miRNA potentially applicable as a predictor for SRNS development in children.
- Trautmann, A.; Schnaidt, S.; Lipska-zi, B.S.; Bodria, M.; Ozaltin, F.; Emma, F.; Anarat, A.; Melk, A.; Azocar, M.; Oh, J.; 2017. Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children. 2017 3055–3065, doi:10.1681/ASN.2016101121.Google Scholar
- Hoefele, J.; Beck, B.B.; Weber, L.T.; Brinkkötter, P. 2018. Steroid-resistent nephrotic syndrome. Medizinische Genet. doi:10.1007/s11825-018-0215-1.Google Scholar
- Srivastava, R..; Aggarwal, V.2012. Steroid Resistant Nephrotic Syndrome in Children. Apollo Med. doi:10.1016/s0976-0016(11)60262-7.Google Scholar
- Hjorten, R.; Anwar, Z.; Reidy, K.J. 2016 Long-term outcomes of childhood onset nephrotic syndrome. Front. Pediatr.Google Scholar
- Rizk, M.K.; El-Nawawy, A.; Abdel-Kareem, E.; Amer, E.S.; El-Gezairy, D.; El-Shafei, A.Z. 2005 Serum interleukins and urinary microglobulin in children with idiopathic nephrotic syndrome. East. Mediterr. Heal. J. 11, 993–1002.Google Scholar
- Argyropoulos, C.P.; Chen, S.S.; Ng, Y.H.; Roumelioti, M.E.; Shaffi, K.; Singh, P.P. 2017 Tzamaloukas, A.H. Rediscovering Beta-2 microglobulin as a biomarker across the spectrum of kidney diseases. Front. Med. 4, doi:10.3389/fmed.2017.00073.Google Scholar
- Xu, D.; Lu, C.; Guo, Y.; Yue, H. 2016 High excretion of urinary beta-2-microglobulin and IgG predicts progressive renal function in idiopathic membranous nephropathy. Int. J. Clin. Exp. Med. 9, 11341–11347.Google Scholar
- Hofstra, J.M.; Deegens, J.K.J.; Willems, H.L.; Wetzels, J.F.M. 2008 Beta-2-microglobulin is superior to N-acetyl-beta-glucosaminidase in predicting prognosis in idiopathic membranous nephropathy. Nephrol. Dial. Transplant. 23, 2546–2551, doi:10.1093/ndt/gfn007.Google ScholarCross Ref
- Yoon SJ, Shin IJ. Lee JS, K.H. 2008 Urinary N-acetyl-beta-D glocosaminidase and beta-2 microglobulin in children with various renal diseases. 2, 143–149.Google Scholar
- Lim, B.J.; Yang, J.W.; Do, W.S.; Fogo, A.B. 2016 Pathogenesis of focal segmental glomerulosclerosis. J. Pathol. Transl. Med. 50, 405–410, doi:10.4132/jptm.2016.09.21.Google ScholarCross Ref
- Fogo, A.B. 2014 Causes and pathogenesis of focal segmental glomerulosclerosis. Nat. Publ. Gr. doi:10.1038/nrneph.2014.216.Google Scholar
- D'agati, V.D.; Kaskel, F.J.; Falk, R.J. 2011 Medical Progress Focal Segmental Glomerulosclerosis. N Engl J Med 365, 2398–411.Google ScholarCross Ref
- He, J.C.; Husain, M.; Sunamoto, M.; Agati, V.D.D.; Klotman, M.E.; Iyengar, R.; Klotman, P.E. 2004 Nef stimulates proliferation of glomerular podocytes through activation of Src- dependent Stat3 and MAPK1 , 2 pathways. 114, doi:10.1172/JCI200421004.The.Google Scholar
- He, L.; Hannon, G.J.; Harbor, C.S. 2004 MicroRNAs: SMALL RNAs WITH A BIG ROLE IN GENE REGULATION. 5, doi:10.1038/nrg1379.Google Scholar
- DG Padmashree,NR Swamy, 2013. Molecular signaling cascade of miRNAs in causing Diabetes Nephropathy. BioinformaticsGoogle Scholar
- Bartel, D.P. 2009 MicroRNAs: Target Recognition and Regulatory Functions. Cell 136, 215–233.Google Scholar
- Bhatt, K.; Kato, M.; Natarajan, R. 2016 Mini-review: emerging roles of microRNAs in the pathophysiology of renal diseases. Am. J. Physiol. Physiol. 310, F109–F118, doi:10.1152/ajprenal.00387.2015.Google ScholarCross Ref
- Friedman, R.C.; Farh, K.K.; Burge, C.B.; Bartel, D.P. 2009 Most mammalian mRNAs are conserved targets of microRNAs. 92–105, doi:10.1101/gr.082701.108.Google Scholar
- Nascimento, L.R. do; Domingueti, C.P. 2019 MicroRNAs: new biomarkers and promising therapeutic targets for diabetic kidney disease. J. Bras. Nefrol. 41, 412–422, doi:10.1590/2175-8239-JBN-2018-0165.Google ScholarCross Ref
- Kato, M.; Castro, N.E.; Natarajan, R. 2013 MicroRNAs: Potential mediators and biomarkers of diabetic complications. Free Radic. Biol. Med. 64, 85–94, doi:10.1016/j.freeradbiomed.2013.06.009.Google ScholarCross Ref
- Livak, K.J.; Schmittgen, T.D. 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402–408, doi:10.1006/meth.2001.1262.Google ScholarCross Ref
- Kim, K.M.; Kim, S.-S.; Kim, H.; Koo, T.; Im, E.Y.; Kim, S.B. 2011 Higher serum beta2-microglobulin levels are associated with better survival in chronic hemodialysis patients: a reverse epidemiology. Clin. Nephrol. 75, 458–465, doi:10.5414/cnp75458.Google ScholarCross Ref
- Herrero-Morín, J.D.; Málaga, S.; Fernández, N.; Rey, C.; Diéguez, M.Á.; Solís, G.; Concha, A.; Medina, A. 2007 Cystatin C and beta2-microglobulin: Markers of glomerular filtration in critically ill children. Crit. Care 11, 1–7, doi:10.1186/cc5923.Google ScholarCross Ref
- Stanga, Z.; Nock, S.; Medina-Escobar, P.; Nydegger, U.E.; Risch, M.; Risch, L. 2013 Factors Other than the Glomerular Filtration Rate That Determine the Serum Beta-2-Microglobulin Level. PLoS One 8, doi:10.1371/journal.pone.0072073.Google Scholar
- D'Agati, V.D.; Kaskel, F.J.; Falk, R.J. 2011 Focal segmental glomerulosclerosis. N. Engl. J. Med. 365, 2398–2411.Google ScholarCross Ref
- Reidy, K.; Kaskel, F.J. 2007 Pathophysiology of focal segmental glomerulosclerosis. Pediatr. Nephrol.Google Scholar
- Zhong, X.; Chung, A.C.K.; Chen, H.-Y.; Meng, X.-M.; Lan, H.Y. 2011 Smad3-mediated upregulation of miR-21 promotes renal fibrosis. J. Am. Soc. Nephrol. 22, 1668–1681, doi:10.1681/ASN.2010111168.Google ScholarCross Ref
- Huang, C.-K.; Bär, C.; Thum, T. 2020 miR-21, Mediator, and Potential Therapeutic Target in the Cardiorenal Syndrome. Front. Pharmacol. 11, 726, doi:10.3389/fphar.2020.00726.Google Scholar
- Mousa, S.O.; Saleh, S.M.; Aly, H.M.; Amin, M.H. 2018 Evaluation of serum soluble urokinase plasminogen activator receptor as a marker for steroid-responsiveness in children with primary nephrotic syndrome. Saudi J. Kidney Dis. Transpl. 29, 290–296, doi:10.4103/1319-2442.229266.Google ScholarCross Ref
- Chau, Y.Y.; Brownstein, D.; Mjoseng, H.; Lee, W.C.; Buza-Vidas, N.; Nerlov, C.; Jacobsen, S.E.; Perry, P.; Berry, R.; Thornburn, A.; 2011 Acute multiple organ failure in adult mice deleted for the developmental regulator Wt1. PLoS Genet. 7, doi:10.1371/journal.pgen.1002404.Google Scholar
- Wang, W.; Liu, R.; Su, Y.; Li, H.; Xie, W.; Ning, B. 2018 MicroRNA-21-5p mediates TGF-β-regulated fibrogenic activation of spinal fibroblasts and the formation of fibrotic scars after spinal cord injury. Int. J. Biol. Sci. 14, 178–188, doi:10.7150/ijbs.24074.Google ScholarCross Ref
- Kölling, M.; Kaucsar, T.; Schauerte, C.; Hübner, A.; Dettling, A.; Park, J.K.; Busch, M.; Wulff, X.; Meier, M.; Scherf, K.; 2017 Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice. Mol. Ther. 25, 165–180, doi:10.1016/j.ymthe.2016.08.001.Google ScholarCross Ref
- Hinkel, R.; Ramanujam, D.; Kaczmarek, V.; Howe, A.; Klett, K.; Beck, C.; Dueck, A.; Thum, T.; Laugwitz, K.-L.; Maegdefessel, L.; 2020 AntimiR-21 Prevents Myocardial Dysfunction in a Pig Model of Ischemia/Reperfusion Injury. J. Am. Coll. Cardiol. 75, 1788–1800, doi:https://doi.org/10.1016/j.jacc.2020.02.041.Google ScholarCross Ref
- Javanmard, S.H.; Vaseghi, G.; Ghasemi, A.; Rafiee, L.; Ferns, G.A.; Esfahani, H.N.; Nedaeinia, R. 2020 Therapeutic inhibition of microRNA-21 (miR-21) using locked-nucleic acid (LNA)-anti-miR and its effects on the biological behaviors of melanoma cancer cells in preclinical studies. Cancer Cell Int. 20, 1–12, doi:10.1186/s12935-020-01394-6.Google ScholarCross Ref
Index Terms
- The Role of miR-21 on the Expression of β2-Microglobulin in Steroid-resistant Nephrotic Syndrome Children
Recommendations
In silico predicted essential genes required for zebrafish (Danio rerio) steroid hormone production
BCB '10: Proceedings of the First ACM International Conference on Bioinformatics and Computational BiologyGenome-scale metabolic models associate genes and transcript enzymes involved in biochemical reactions. We present a genome-scale stoichiometric reconstruction of the zebrafish (Danio rerio) steroidogenic network and apply linear programming methods to ...
Comments