miRNAs involved in the TGFB signaling as possible markers of steroid-resistant nephrotic syndrome in children

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-02-19 DOI:10.1016/j.genrep.2025.102173

Ahmedz Widiasta , Yunia Sribudiani , Husna Nugrahapraja , Dedi Rachmadi

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Abstract

Introduction

Steroid-resistant nephrotic syndrome (SRNS) and subsequent chronic kidney disease (CKD) cause morbidity and mortality in children. Transforming growth factor-β (TGFB) participates in the development of focal segmental glomerulosclerosis (FSGS), the most common histopathological form of SRNS. This study demonstrated a correlation between the levels of blood TGFB and its related microRNAs (miRNAs) in children with SRNS.

Materials and methods

This was an open-prospective cohort study conducted at Hasan Sadikin General Hospital, Bandung, Indonesia. Of 188 children with nephrotic syndrome (NS), 24 (aged 1–18 years) were enrolled, only those who had never received steroids. Blood samples were collected before treatment with steroids or other immunosuppressants. Steroid resistance was diagnosed after four weeks of follow-up. SRNS was defined as persistent proteinuria after treatment with prednisolone or methylprednisolone. Blood levels of miRNAs of interest and the expression were measured using qRT-PCR (TaqMan miRNA Assay).

Results

There was a significant increase in miR-433 and TGFB2 expression in SRNS (p = 0.030 and p = 0.001, respectively). Meanwhile, there were no significant correlations between miR-21, miR-29, miR-200, miR-205, and miR-433 and TGFB1 and TGFB2.

Conclusions

MiR-433 is potentially involved in SRNS, TGFB2 baseline is a promising biomarker for predicting steroid resistance in SRNS, and antimiR-433 is promising as the next proposed study to discover novel SRNS therapies.

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参与TGFB信号传导的mirna可能是儿童激素抵抗性肾病综合征的标志物

激素抵抗性肾病综合征（SRNS）和随后的慢性肾脏疾病（CKD）导致儿童发病率和死亡率。转化生长因子-β (TGFB)参与局灶节段性肾小球硬化（FSGS）的发展，这是SRNS最常见的组织病理学形式。本研究证实了SRNS患儿血液TGFB水平与其相关的microRNAs （miRNAs）之间的相关性。材料和方法这是一项在印度尼西亚万隆的Hasan Sadikin总医院进行的开放前瞻性队列研究。188名患有肾病综合征（NS）的儿童中，24名（1-18岁）被纳入研究，这些儿童从未接受过类固醇治疗。在使用类固醇或其他免疫抑制剂治疗前采集血样。随访4周后诊断为类固醇抵抗。SRNS定义为强的松龙或甲基强的松龙治疗后的持续性蛋白尿。使用qRT-PCR （TaqMan miRNA Assay）测量感兴趣的miRNA的血液水平和表达。结果miR-433和TGFB2在SRNS中的表达显著升高（p = 0.030和p = 0.001）。同时，miR-21、miR-29、miR-200、miR-205、miR-433与TGFB1、TGFB2之间无显著相关性。结论smir -433可能参与SRNS， TGFB2基线是预测SRNS中类固醇耐药的有希望的生物标志物，而anti -433有望成为下一个发现新的SRNS治疗方法的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.