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03 June 2020 : Clinical Research  

Absence of Long Noncoding RNA H19 Promotes Childhood Nephrotic Syndrome through Inhibiting ADCK4 Signal

Jinwen Xu1ABCDEFG*, Tingting Ge1B, Hongxia Zhou1C, Lin Zhang1CE, Liping Zhao1ABCDEFG

DOI: 10.12659/MSM.922090

Med Sci Monit 2020; 26:e922090


BACKGROUND: Nephrotic syndrome (NS) is a common chronic kidney disease in children characterized by a group of clinical symptoms such as massive proteinuria, hypoproteinemia, high edema, and hyperlipidemia. Despite the tremendous efforts already made, the diagnosis for nephrotic syndrome still remains poor in children.

MATERIAL AND METHODS: The blood samples from 30 healthy children and 30 children with nephrotic syndrome were collected. The expression of H19 and ADCK4 (which are genes recently identified to play key roles in the development of nephrotic syndrome) in peripheral blood mononuclear cells (PBMCs), were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression of ADCK4 was also detected by RT-qPCR or western blot when H19 was overexpressed or knocked down in human primary renal podocytes. Luciferase activity analysis was performed to measure whether H19 could regulate the promoter activity of ADCK4. RNA pull-down. In addition, mass spectrometry assay was used to find the transcription factor which could bind with H19, and RNA immunoprecipitation assay (RIPA) analysis was done to further confirm the interaction between H19 and candidate transcription factor.

RESULTS: Long noncoding RNA H19 (lncRNA H19) expression was downregulated in PBMCs of children with nephrotic syndrome. ADCK4 was also downregulated. In human primary renal podocytes, overexpression of H19 promoted the expression of ADCK4, while H19 knockdown inhibited it. Furthermore, our study demonstrated that H19 could regulate the promoter activity of ADCK4. Using RNA pull-down and mass spectrometry technology, we found the transcription factor-THAP1 could bind with H19, and the interaction between them was further confirmed by RIPA analysis.

CONCLUSIONS: H19 expression in blood samples may be a novel marker of the diagnosis of nephrotic syndrome in children.

Keywords: Adult Children, nephrotic syndrome, RNA, Long Noncoding, Apoptosis Regulatory Proteins, Child, DNA-Binding Proteins, Kidney, Mass Spectrometry, Mutation, Podocytes, Protein Kinases, Renal Insufficiency, Chronic, Signal Transduction



01 August 2022 : Editorial  

Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937927

Med Sci Monit 2022; 28:e937927

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750