University of Leicester
2021BhachuJPhD.pdf (3.87 MB)

The role of circulating microRNAs in the pathogenesis of IgA nephropathy

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posted on 2022-02-11, 12:33 authored by Jasraj Singh Bhachu
IgA nephropathy (IgAN) is the commonest form of primary glomerulonephritis worldwide with approximately 30% of patients developing end stage renal disease (ESRD) within 10 years of diagnosis and requiring renal replacement therapy. Clinically, there is no cure for IgAN and there is no reliable method to predict this progression early on in the disease course. IgAN is defined by the predominant deposition of IgA in the glomerular mesangium which is also commonly observed complexed with other co-deposits including IgG, IgM or complement proteins. Since IgAN is considered to be a systemic disease with the kidneys being injured as innocent bystanders, investigation of circulating markers as a key to its pathogenesis is well founded. Recently, the emergence of microRNAs (miRs) as negative regulators of gene expression have opened new avenues to understand their role, as biomarkers, in normal and disease pathological processes including IgAN. In this study, next generation sequencing (NGS) and subsequent validation by RT-qPCR revealed two miRs (miRs -483-5p and -122-5p) as potential prognostic markers in IgAN. More importantly, identification of these miRs in exosomes found that both miRs -483-5p and -122-5p were increased in those patients at a higher risk of progressing to ESRD compared to those with the stable form of the disease. Correlation statistics showed that exosomal levels of both miRs -483-5p and -122-5p correlated with the tumour necrosis factor (TNF) superfamily analytes. Investigation into the source of the miRs revealed that miR-483-5p but not miR-122-5p was expressed in B cells. Studies, in vitro, showed that stimulating immortalised B cells with TNF super family analytes TNFR1 and CD27 elicited B cell activation and increased levels of miR-483-5p in B cell-derived extracellular microvesicles. These miR-483-5p enriched B cell vesicles interacted with collecting duct epithelial cells (CDECs) to induce an inflammatory response. Additionally, the transcription factor SOCS3, a known target of miR-483-5p identified in silico, was found to be suppressed in CDECS. The results of this study have indicated a potentially new avenue for investigating the pathogenesis of IgAN.



Izabella Pawluczyk; Jonathan Barratt

Date of award


Author affiliation

Department of Respiratory Sciences

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD



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