MicroRNAs in IgA nephropathy

Yao, Xingchen; Zhai, Yunkai; An, Huanping; Gao, Jingge; Chen, Yazhuo; Zhang, Wenhui; Zhao, Zhanzheng

doi:10.1080/0886022x.2021.1977320

Cited by 12 publications

(13 citation statements)

References 72 publications

(117 reference statements)

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“…miRNAs have a vital role in regulating various cellular processes, such as cell migration, proliferation and apoptosis. miRNAs are stable, ubiquitous and abundant in body fluids and cells; hence, miRNAs may be considered good biomarkers as well as drug targets (28,29). According to previous studies, miR-148b, let7b, miR-146a, miR-155, miR-21, miR-200 and miR-429 miRNAs may be involved in IgAN development (30).…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, small RNA-seq was performed for the identification of additional functional miRNAs and the results demonstrated that nearly 75% of miRNAs were present in renal tissues from both healthy individuals and patients with IgAN. Among the 25 significant DEMs, miR-21-5p (31,32) and miR-155-5p (22,28) were previously reported to be associated with IgAN. However, the other three miRNAs, miR-146a, miR-192 and miR-146b, were newly identified in patients with IgAN.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNAs as a therapeutic target in IgA nephropathy in Indian population

et al. 2023

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Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease with rapid development to end stage renal disease, requiring renal replacement therapy. Genome-wide studies suggest geographical variations in genetic susceptibility to IgAN and disease progression. Specific 'candidate genes' were indicated to correlate with different functions that are involved in the pathogenesis of renal conditions. MicroRNAs (miRNAs/miRs) have a major role in mRNA degradation or translation repression, thereby regulating the expression of their target proteins. Previously, a small number of miRNAs were reported to have direct associations with IgAN. In the present study, new miRNAs linked to IgAN were identified in the Indian population. The miRNA was isolated from kidney biopsies of patients with IgAN (n=6) and healthy control tissue from patients with renal cell carcinoma (n=6). The sequencing results indicated that the miRNA percentage acquired from controls and patients with IgAN was 5.61 and 4.35%, respectively. From the results, 10 upregulated and 15 downregulated miRNAs were identified. Of the 25 differentially expressed miRNAs (DEMs), miR-181a-5p, miR-28-3p, let-7g-5p, miR-92a-3p and miR-30c-5p were not reported previously. Furthermore, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses suggested that the target genes of the DEMs were mainly enriched in pathways such as cancer, ErbB signalling, proteoglycans in cancer, Hippo signalling and MAPK pathways. The newly identified miRNAs may impact the behaviour of tissues or IgA deposition by regulating signalling pathways, which forms a basis for future studies aimed at improving the diagnosis and care of patients with IgAN in the Indian community.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNAs as a therapeutic target in IgA nephropathy in Indian population

et al. 2023

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“…The expression levels of urinary exosomal miRNAs have been examined as surrogates of disease progression in several diseases, however, this is the rst study to differentiate IgAN-speci c miRNAs in human urine exosomes [14][15][16][17]. In this study, miR-199a-3p was the leading urinary exosomal miRNA in terms of its prognostic value for clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Urinary Exosomal microRNAs in patients with IgA nephropathy

Yoon

Kim

Jung

et al. 2023

Preprint

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Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN. Methods: From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathological features. The primary endpoint of this study was to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN. Results: IgAN group showed dysregulated urinary exosomal miRNA levels compared with the normal and disease control groups. Urinary exosomal miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular ﬁltration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate analysis, age, body mass index, hypertension, eGFR, uPCR, and five miRNAs (miR-16-5p, miR-29a-3p, miR-124-3p, miR-199a-3p, and miR-335-3p) were signiﬁcantly associated with disease progression in patients with IgAN. MiR-199a-3p with the lowest p-value in disease progression analysis, showed an area under the curve (AUC) of 0.727, while the AUC of miR-124-3p, with the second lowest p-value, was 0.718. When these two miRNAs were combined, the AUC was high enough (0.786), considering that the AUC of the International IgAN Risk Prediction Tool was 0.890. Conclusion: Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN. Further studies are needed to elucidate the physiological mechanisms and clarify the results of this study.

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“…IgA nephropathy (IgAN) is one of the most common primary glomerulopathies worldwide [1], and is characterized by a variable clinical course ranging from a benign condition to rapid progression to renal failure. Specifically, 15–40% of patients will develop end-stage renal disease (ESRD) within 10–20 years of onset [2].…”

Section: Introductionmentioning

confidence: 99%

Renal Megalin mRNA Downregulation Is Associated with CKD Progression in IgA Nephropathy

Wen¹,

Wang²,

Ji³

et al. 2022

Am J Nephrol

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Introduction: Megalin plays an important role in proximal tubule uptake of filtered proteins. Downregulation and dysfunction of megalin were previously demonstrated in IgA nephropathy (IgAN); however, its relationship to IgAN progression remains unclear. Methods: We measured renal megalin mRNA and miR-148b, previously identified as a regulator of megalin, in a retrospective cohort of 417 IgAN patients at the time of biopsy, and evaluated their associations with chronic kidney disease (CKD) progression event, defined as end-stage renal disease or ≥40% decline in estimated glomerular filtration rate, using Cox proportional hazard models. Risk classification statistics were calculated for CKD progression. Results: During a median follow-up of 43 months, 121 (29.0%) patients reached the CKD progression event. Patients in the highest tertile of renal megalin mRNA had a lower risk for CKD progression than in the lowest tertile (hazard ratio (HR): 0.407, 95% confidence interval (CI) 0.231–0.719; p = 0.002). Log megalin mRNA was independent and negatively associated with CKD progression in IgAN (HR: 0.529, 95% CI 0.377–0.742; p < 0.001). The addition of renal megalin mRNA to a model with traditional risk factors improved risk prediction of disease progression (C statistic from 0.76 to 0.80; integrated discrimination index: 0.04 [95% CI: 0.02–0.07]). Moreover, patients in the highest tertile of renal miR-148b had a 2.3-fold higher risk for CKD progression compared with those in the lowest tertile. Conclusions: Lower renal megalin mRNA levels were associated with a greater risk of CKD progression in IgAN independent of clinical and pathological characteristics, suggesting that renal megalin could be an important prognostic factor for IgAN.

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MicroRNAs in IgA nephropathy

Cited by 12 publications

References 72 publications

MicroRNAs as a therapeutic target in IgA nephropathy in Indian population

MicroRNAs as a therapeutic target in IgA nephropathy in Indian population

Clinical Significance of Urinary Exosomal microRNAs in patients with IgA nephropathy

Renal Megalin mRNA Downregulation Is Associated with CKD Progression in IgA Nephropathy

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