Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson–Fabry disease

Salamon, Irene; Biagini, Elena; Kunderfranco, Paolo; Roncarati, Roberta; Ferracin, Manuela; Taglieri, Nevio; Nardi, Elena; Laprovitera, Noemi; Tomasi, Luciana; Santostefano, Marisa; Ditaranto, Raffaello; Vitale, Giovanni; Pisani, Antonio; Riccio, Eleonora; Aiello, Valeria; Capelli, Irene; Galiè, Nazzareno; Spinelli, Letizia; Condorelli, Gianluigi

doi:10.1038/s41419-021-04438-5

Cited by 9 publications

(7 citation statements)

References 62 publications

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“…Moreover, our findings are in agreement with a recent investigation indicating that miR-184 levels are altered in FD patients (Salamon et al, 2021); indeed, miR-184 is known to target another gene that is crucial for mitochondrial function, namely Slc25a22 (Morita et al, 2013), a mitochondrial carrier that transports glutamate (Goubert et al, 2017) and asymmetric dimethyl L-arginine (Porcelli et al, 2016). Our results call for future investigations in this direction, unveiling the essential role of mitochondria as a new frontier in FD research.…”

Section: Discussionsupporting

confidence: 92%

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Gambardella

Fiordelisi

Sorriento

et al. 2022

J Pharmacol Exp Ther

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We demonstrate for the first time that a specific signature of circulating mitochondrial microRNAs (mitomiRs) is dysregulated in Fabry disease (FD). In our study, we observed that mitomiRs regulating fundamental aspects of mitochondrial homeostasis and fitness, including expression and assembly of the respiratory chain, mitogenesis, antioxidant capacity, and apoptosis are significantly dysregulated in FD patients. Taken together, our new findings introduce mitomiRs as unprecedented biomarkers of FD and point at mitochondrial dysfunction as a novel potential mechanistic target for therapeutic approaches.

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Section: Discussionsupporting

confidence: 92%

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Gambardella

Fiordelisi

Sorriento

et al. 2022

J Pharmacol Exp Ther

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“… 23 , 24 Additionally, miR-184, let-7a, and let-7d have been reported to be beneficial in diagnosing and treating Fabry disease, a hereditary cerebral small vessel disease. 25 , 26 Nevertheless, the study of circulating exosomal miRNAs in CSVD is still in its infancy. In the few studies published so far, exosomal miRNA-17 family and miR-223-3p were proved to be closely related to the initiation and development of CSVD.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exosomal miR-320e as a Novel Potential Biomarker for Cerebral Small Vessel Disease

Gao¹,

Yin²,

Wang³

et al. 2023

IJGM

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Background Cerebral small vessel disease (CSVD) with an insidious onset can cause overall neurological dysfunction and dementia, bringing a massive burden to society. However, the pathogenesis of CSVD is complex and reliable non-invasive biomarkers for diagnosis are still not available at present. Our study aimed to investigate abnormal exosomal miRNA patterns via microarray analysis and identify candidate biomarkers for CSVD. Methods We isolated exosomes from the plasma of all subjects and identified exosomes via currently universally accepted methods. The miRNAs were profiled through microarrays, and then the expression of selected differentially expressed miRNAs was validated through RT-PCR. GO and KEGG analysis predicted possible functions of differentially expressed miRNAs. Receiver operating characteristic (ROC) curve was employed to observe the diagnostic value of selective miRNAs. Finally, the relationship between the expression of miR-320e and the CSVD burden was analyzed. Results A total of 14 miRNAs displayed differential enrichment levels with |fold change|≥1.5 and p<0.05 through miRNA microarray analysis. The RT-PCR analysis validated that exosomal miR-320e was significantly downregulated in CSVD patients (p<0.0001). ROC curve analysis of exosomal miR-320e showed the area under the curve of 0.752. According to the multivariable analysis, miR-320e was an independent predictor of white matter hyperintensity ([aOR]= 0.452, 95% confidence interval [CI]= 0.258–0.792, p=0.006) and exhibited a negative correlation with the load of periventricular white matter hyperintensities (p=0.0021) and deep white matter hyperintensities (p=0.0018), respectively. In addition, it exhibited a negative correlation with total CSVD burden score (r=−0.276, p=0.001). Conclusion In our study, plasma exosomal miR-320e has a certain diagnostic value for CSVD, and a significant correlation with imaging burden of CSVD. Overall, exosomal miR-320e has the potential to be a novel biomarker for CSVD, but further research with a large sample size is necessary to assess its clinical utility.

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“…miR-184 is a vital member of miRNAs. It has elevated expression in patients with renal carcinoma [ 9 ] and serves as a predictive biomarker of cardiac damage [ 10 ]. Additionally, miR-184 showed altered expression in 8-month-old Zucker diabetic fatty (ZDF) rats and enhanced renal fibrosis [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Downregulating miR-184 relieves calcium oxalate crystal-mediated renal cell damage via activating the Rap1 signaling pathway

Han,

Zhang,

et al. 2023

Aging

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Background: Renal calculi are a very prevalent disease with a high incidence. Calcium oxalate (CaOx) is a primary constituent of kidney stones. Our paper probes the regulatory function and mechanism of miR-184 in CaOx-mediated renal cell damage. Methods: CaOx was used to treat HK2 cells and human podocytes (HPCs) to simulate kidney cell damage. The qRT-PCR technique checked the profiles of miR-184 and IGF1R. The examination of cell proliferation was conducted employing CCK8. TUNEL staining was used to monitor cell apoptosis. Western blot analysis was used to determine the protein profiles of apoptosis-concerned related proteins (including Mcl1, Bcl-XL, and Caspase-3), the NF-κB, Nrf2/HO-1, and Rap1 signaling pathways. ELISA confirmed the levels of the inflammatory factors IL-6, TNF-α, MCP1, and ICAM1. The targeting relationship between miR-184 and IGF1R was validated by dual luciferase assay and RNA immunoprecipitation assay. Results: Glyoxylate-induced rat kidney stones model and HK2 and HPC cells treated with CaOx demonstrated an increase in the miR-184 profile. Inhibiting miR-184 relieved CaOx-mediated renal cell inflammation, apoptosis and oxidative stress and activated the Rap1 pathway. IGF1R was targeted by miR-184. IGF1R activation by IGF1 attenuated the effects of miR-184 on renal cell damage, and Hippo pathway suppression reversed the inhibitory effect of miR-184 knockdown on renal cell impairment. Conclusions: miR-184 downregulation activates the Rap1 signaling pathway to ameliorate renal cell damage mediated by CaOx.

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Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson–Fabry disease

Cited by 9 publications

References 62 publications

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Mitochondrial microRNAs Are Dysregulated in Patients with Fabry Disease

Exosomal miR-320e as a Novel Potential Biomarker for Cerebral Small Vessel Disease

Downregulating miR-184 relieves calcium oxalate crystal-mediated renal cell damage via activating the Rap1 signaling pathway

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