In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy

Serino, Grazia; Pesce, Francesco; Sallustio, Fabio; Palma, Giuseppe De; Cox, Sharon Natasha; Curci, Claudia; Zaza, Gianluigi; Lai, Kar Neng; Leung, Joseph C.K.; Tang, Sydney C.W.; Papagianni, Αikaterini; Stangou, Maria; Goumenos, Dimitrios; Gerolymos, Miltiadis; Takahashi, Kazuo; Yuzawa, Yukio; Maruyama, Shoichi; Imai, Enyu; Schena, Francesco Paolo

doi:10.1038/ki.2015.333

Cited by 74 publications

(62 citation statements)

References 45 publications

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“…A selection bias was present in this study. Patients experienced rather milder renal impairment compared to similar studies in IgA by other scholars [40,51]. This could explain why we did not observe much glomerular sclerosis instead of IFTA lesions, which was also an additional reason for our lack of outcome event observations.…”

Section: Discussioncontrasting

confidence: 42%

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Fan

Zhu

et al. 2019

Nephron

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Background/Aims: Clinical manifestation and renal histology serve as the current “gold standard” for evaluation of renal lesions in IgA nephropathy. MiR-192 is regarded as a potential noninvasive biomarker for kidney disease. We sought to elucidate a relationship between intrarenal, serum, and urinary exosomal miR-192 with renal lesions and disease progression in IgA nephropathy. Methods: Serum and urinary exosomal miR-192 were detected and correlated with clinical and pathological parameters from consecutive IgA nephropathy patients (n = 50) and healthy control patients (n = 25). Patients then received a follow-up of 24 months after biopsy. Disease progression was defined as a 40% reduction in estimated glomerular filtration rate. Expression of miR-192 was quantified by Taqman RT-PCR. Intrarenal miR-192 was detected in 8 IgA nephropathy patients and 4 matched patients receiving kidney nephrectomy as controls via in situ hybridization. TGF-β1 and E-cadherin expression in renal tissue was evaluated using immunohistochemistry. Results: Intrarenal miR-192 was correlated with serum miR-192 (r = 0.690, p = 0.013). Both intrarenal and serum miR-192 decreased in IgA nephropathy patients and were correlated with estimated glomerular filtration ratio. Patients with lower intrarenal and serum miR-192 levels had a higher interstitial fibrosis and tubular atrophy score, more severe lesions in tubular atrophy, and interstitial inflammation. Renal E-cadherin expression was correlated (r = 0.484, p = 0.004) and TGF-β1 was inversely correlated (r = –0.527, p < 0.001) with serum miR-192 in IgA. Patients with higher serum miR-192 had a lower disease progression rate over the course of 2 years (0 vs. 16%, p = 0.028). No correlation was found in urinary exosomal miR-192 with the clinical and pathological parameters mentioned earlier. Conclusions: Lower serum miR-192 in IgA nephropathy patients indicates lower intrarenal miR-192 expression, more severe tubular atrophy, interstitial inflammation, and fibrotic tendency (with higher TGF-β and E-cadherin in renal miR-192). IgA nephropathy patients with higher serum miR-192 are less likely to have renal function decline over the course of 2 years.

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Section: Discussioncontrasting

confidence: 42%

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Fan

Zhu

et al. 2019

Nephron

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“…Two miRNAs, miR-148b and let-7b, which seem to mediate the aberrant O-glycosylation process of IgA and that can differentiate IgA nephropathy patients in serum tests5960, were not significantly expressed in our cohort. In other diseases like in acute leukemia or gastric cancer it has been shown that serum levels of miRNA expression were not the same as in tissue samples6162.…”

Section: Discussionmentioning

confidence: 60%

Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy

Bockmeyer

Säuberlich

Wittig

et al. 2016

Sci Rep

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Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5). Laser-microdissected glomeruli were used for expression profiling of 762 miRNAs by low-density TaqMan arrays (cards A and B). The comparison of different normalization methods (GeNormPlus, NormFinder, global mean and snoRNAs) in crescentic IgA-GN, IgA-GN and controls yielded similar results. However, levels of significance and the range of relative expression differed. In median, two normalization methods demonstrated similar results. GeNormPlus and NormFinder gave different top ranked reference miRNAs. Stability ranking for snoRNAs varied between cards A and B. In conclusion, we suggest the geometric mean of the most stable reference miRNAs found in GeNormPlus (miR-26b-5p), NormFinder (miR-28-5p) and snoRNAs (RNU44) as reference. It should be considered that significant differences could be missed using one particular normalization method. As a starting point for glomerular miRNA studies in IgA nephropathy we provide a library of miRNAs.

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“…A large number of studies [36-38] comfirm that miRNAs can be biomarkers of IgA nephropathy, such as miR-148b, let-7b, miR-3613-3p, miR-200a, miR-200b, and so on. Due to being non-invasive and easily obtained, urinary sediment miRNAs have become a new direction for searching for non-invasive biomarkers of IgAN.…”

Section: Erythrocyte-derived Mirnas Can Be Specific Biomarkers Of Iganmentioning

confidence: 99%

Urinary Erythrocyte-Derived miRNAs: Emerging Role in IgA Nephropathy

Duan¹,

Cai²,

Li³

et al. 2017

Kidney Blood Press Res

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Hematuria is one of the basic clinical manifestations of IgA nephropathy (IgAN). Isolated microscopic hematuria or microscopic hematuria combined with proteinuria is risk factor for the long-term prognosis of IgAN. Current evidence of the consequences of glomerular hematuria rests on insights from basic research on the molecular mechanisms of hemoglobin and related reactive oxygen species-induced tubular injury as well as on the clinical evidence of macroscopic hematuria–associated acute kidney injury (AKI) in IgAN. These researches may simply elucidate some effects of macroscopic hematuria but not microscopic hematuria. Recent studies conducted on blood and urinary erythrocytes have made progress. Researches have revealed that mature erythrocytes contain abundant, long, non-coding RNA, miRNA (microRNA) and Y RNA. Among the top 50 expressions of erythrocyte-derived miRNAs, 33 (66%) of them may be the potential urinary biomarkers of IgAN. Moreover, when urinary erythrocytes are compressed while exiting out of an impaired nephron, erythrocyte-derived vesicles (including microvesicles and apoptotic vesicles) may increase. Animal models for hematuria and human biopsy tissues confirm renal parenchymal cells could phagocytose red blood cells and erythrocyte-derived vesicles. These vesicles, which contain miRNAs, may alter the transcriptome of recipient cells and impact the occurrence and development of IgAN.

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In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy

Cited by 74 publications

References 45 publications

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Serum miR-192 Is Related to Tubulointerstitial Lesion and Short-Term Disease Progression in IgA Nephropathy

Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy

Urinary Erythrocyte-Derived miRNAs: Emerging Role in IgA Nephropathy

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