MicroRNA Expression Profiling in Diabetic Kidney Disease

Ishii, Hiroki; Kaneko, Shohei; Yanai, Katsunori; Aomatsu, Akinori; Hirai, Keiji; Ookawara, Susumu; Morishita, Yoshiyuki

doi:10.1016/j.trsl.2021.05.008

Cited by 15 publications

(15 citation statements)

References 41 publications

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“…The expression level of one miRNA (miRNA-503-5p) that we observed was differentially expressed in kidneys of the present study's age-dependent renal impairment mice was also evaluated in kidneys of other model mice of kidney diseases by qRT-PCR: a model of diabetic kidney disease (DKD) (db/db mice) (15), a model of renal fibrosis caused by UUO (6), a model of acute kidney injury (ischemiareperfusion injury; IRI) (16), a model of focal segmental glomerulosclerosis (FSGS) generated by adriamycin intravenous injection (17), and a model of immunoglobulin A nephropathy (HIGA/NscSlc) (18). The expression level of miRNA-503-5p differed between the DKD, UUO, and FSGS mice and the respective groups of control mice (Figures 4A-C), while it did not differ between the IRI and HIGA mice and the respective control groups (Figures 4D,E).…”

Section: Mirna-503-5p Expression In the Kidney Of Other Model Micementioning

confidence: 97%

MicroRNA Expression Profiling in Age-Dependent Renal Impairment

et al. 2022

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BackgroundAge-dependent renal impairment contributes to renal dysfunction in both the general population and young and middle-aged patients with renal diseases. Pathological changes in age-dependent renal impairment include glomerulosclerosis and tubulointerstitial fibrosis. The molecules involved in age-dependent renal impairment are not fully elucidated. MicroRNA (miRNA) species were reported to modulate various renal diseases, but the miRNA species involved in age-dependent renal impairment are unclear. Here, we investigated miRNAs in age-dependent renal impairment, and we evaluated their potential as biomarkers and therapeutic targets.MethodsWe conducted an initial microarray profiling analysis to screen miRNAs whose expression levels changed in kidneys of senescence-accelerated resistant (SAMR1)-10-week-old (wk) mice and SAMR1-50wk mice and senescence-accelerated prone (SAMP1)-10wk mice and SAMP1-50wk mice. We then evaluated the expressions of differentially expressed miRNAs in serum from 13 older patients (>65 years old) with age-dependent renal impairment (estimated glomerular filtration ratio <60 mL/min/1.73 m2) by a quantitative real-time polymerase chain reaction (qRT-PCR) and compared the expressions with those of age-matched subjects with normal renal function. We also administered miRNA mimics or inhibitors (5 nmol) with a non-viral vector (polyethylenimine nanoparticles: PEI-NPs) to SAMP1-20wk mice to investigate the therapeutic effects.ResultsThe qRT-PCR revealed a specific miRNA (miRNA-503-5p) whose level was significantly changed in SAMP1-50wk mouse kidneys in comparison to the controls. The expression level of miRNA-503-5p was upregulated in the serum of the 13 patients with age-dependent renal impairment compared to the age-matched subjects with normal renal function. The administration of a miRNA-503-5p-inhibitor with PEI-NPs decreased the miRNA-503-5p expression levels, resulting in the inhibition of renal fibrosis in mice via an inhibition of a pro-fibrotic signaling pathway and a suppression of glomerulosclerosis in mice by inhibiting intrinsic signaling pathways.ConclusionThe serum levels of miRNA-503-5p were decreased in patients with age-dependent renal impairment. However, inhibition of miRNA-503-5p had no effect on age-dependent renal impairment, although inhibition of miRNA-503-5p had therapeutic effects on renal fibrosis and glomerulosclerosis in an in vivo animal model. These results indicate that miRNA-503-5p might be related to age-dependent renal impairment.

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Section: Mirna-503-5p Expression In the Kidney Of Other Model Micementioning

confidence: 97%

MicroRNA Expression Profiling in Age-Dependent Renal Impairment

et al. 2022

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“…4 miRNA has a critical role in maintaining normal organ development and homeostasis by partially complementing the specific mRNA 3′-UTR to regulate the expression of downstream target proteins and then participate in basic biological processes. 5 A previous study suggested an association between miR-124 and the onset of kidney disease and diabetes. 6,7 miR-124 is abnormally expressed in patients with renal disease and ischemic stroke complicated with diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…MicroRNA, a non‐coding single‐stranded RNA molecule with a length of about 20–24 bp nucleotide, participates in the progression of chronic kidney disease by regulating mitochondrial function 4 . miRNA has a critical role in maintaining normal organ development and homeostasis by partially complementing the specific mRNA 3′‐UTR to regulate the expression of downstream target proteins and then participate in basic biological processes 5 . A previous study suggested an association between miR‐124 and the onset of kidney disease and diabetes 6,7 .…”

Section: Introductionmentioning

confidence: 99%

miR‐124‐3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

Liang

Yuan

et al. 2023

The FASEB Journal

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Diabetic kidney disease (DKD) is one of the most serious complications of diabetes mellitus (DM) and the main cause of end‐stage renal failure. However, the pathogenesis of DKD is complicated. In this study, we found that miR‐124‐3p plays a key role in regulating renal mitochondrial function and explored its possible mechanism in DKD progression by performing a series of in vitro and in vivo experiments. Decreased expression of miR‐124‐3p was found in db/db mice compared to db/m mice. Moreover, miR‐124‐3p down‐regulated FOXQ1 by targeting FOXQ1 mRNA 3′‐UTR in NRK‐52E cells. Also, an increase in FOXQ1 and down‐regulation of Sirt4 were found in db/db mouse kidney and renal tubular epithelial cells cultured with high glucose and high lipid. Overexpression of FOXQ1 could further down‐regulate the expression of Sirt4 and aggravate the damage of mitochondria. Conversely, the knockdown of the FOXQ1 gene induced Sirt4 expression and partially restored mitochondrial function. To verify the effects of miR‐124‐3p on Sirt4 and mitochondria, we found that miR‐124‐3p mimics could up‐regulate Sirt4 and inhibit ROS production and MitoSOX, thus restoring the number and morphology of mitochondria. These results showed that under high‐glucose and high‐lipid conditions, the down‐regulation of miR‐124‐3p induces FOXQ1 in renal tubular epithelial cells, which in turn suppresses Sirt4 and leads to mitochondrial dysfunction, promoting the development of DKD.

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“…To date, most evidence in this attractive research area is based on adult [ 36 , 37 , 38 , 39 , 40 ] and in vitro studies [ 27 , 28 , 41 , 42 ], while similar pediatric data are still limited [ 43 , 44 , 45 , 46 , 47 ]. Due to the urgent need for early identification of DN and of the fragmentariness of data in the field in childhood, we attempted to provide a comprehensive pediatric overview on the challenging role of miRNAs in DN.…”

Section: Introductionmentioning

confidence: 99%

Pediatric Diabetic Nephropathy: Novel Insights from microRNAs

Lanzaro

Barlabà

Nigris

et al. 2023

JCM

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Diabetic nephropathy (DN) represents the most common microvascular complication in patients with diabetes. This progressive kidney disease has been recognized as the major cause of end-stage renal disease with higher morbidity and mortality. However, its tangled pathophysiology is still not fully known. Due to the serious health burden of DN, novel potential biomarkers have been proposed to improve early identification of the disease. In this complex landscape, several lines of evidence supported a critical role of microRNAs (miRNAs) in regulating posttranscriptional levels of protein-coding genes involved in DN pathophysiology. Indeed, intriguing data showed that deregulation of certain miRNAs (e.g., miRNAs 21, -25, -92, -210, -126, -216, and -377) were pathogenically linked to the onset and the progression of DN, suggesting not only a role as early biomarkers but also as potential therapeutic targets. To date, these regulatory biomolecules represent the most promising diagnostic and therapeutic options for DN in adult patients, while similar pediatric evidence is still limited. More, findings from these elegant studies, although promising, need to be deeper investigated in larger validation studies. In an attempt to provide a comprehensive pediatric overview in the field, we aimed to summarize the most recent evidence on the emerging role of miRNAs in pediatric DN pathophysiology.

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MicroRNA Expression Profiling in Diabetic Kidney Disease

Cited by 15 publications

References 41 publications

MicroRNA Expression Profiling in Age-Dependent Renal Impairment

MicroRNA Expression Profiling in Age-Dependent Renal Impairment

miR‐124‐3p improves mitochondrial function of renal tubular epithelial cells in db/db mice

Pediatric Diabetic Nephropathy: Novel Insights from microRNAs

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