Comprehensive analysis of microRNA expression and target prediction in children with Nephrotic syndrome (original) (raw)
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2021
Background Recently, urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases and they exhibit great potential as noninvasive biomarkers for the diagnosis of various diseases. The present study was aimed to evaluate the expression status of selected miRNAs (miR-1, miR-215-5p, miR-335-5p and let-7a-5p) in urine samples from children with NS [steroid sensitive (SSNS)] and [steroid resistant (SRNS)] along with healthy control group.Methods MicroRNA isolation was carried out in urine samples collected from SSNS (100 nos), SRNS (100 nos), and healthy controls (50 nos) using MiRNeasy Mini Kit, followed by cDNA conversion for all the four selected miRNAs using Taqman advanced miRNA cDNA synthesis kit and their expression was quantified by Taqman Advanced miRNA assay kits using Real Time PCR Machine and Rotogen-Q in SSNS and SRNS patients and healthy control subjects.ResultsQuantification of all the four miRNAs (miR-1,...
MicroRNAs in kidney function and disease
Translational Research, 2011
MicroRNAs (miRNA) are short non-coding RNA sequences that regulate gene expression by blocking protein translation or inducing mRNA degradation. miRNA is found in various tissues with variable expression and changes in expression are related to various disease processes. Evidence suggests that changes in miRNA expression are critical for the normal development of kidney tissue. Alternatively, in diseases such as diabetic nephropathy, polycystic kidney disease, and lupus nephritis, specific miRNAs may enhance disease manifestations in a myriad of ways, ranging from activation of fibrotic pathways to anatomical changes that abet proteinuria. The variable expression of miRNA in kidney tissue, whether in the context of normal development or disease processes, makes miRNAs a valuable new tool for understanding, diagnosing, and discovering therapeutic options for pathological processes that affect the kidney.
Serum microRNAs are altered in various stages of chronic kidney disease: a preliminary study
Clinical Kidney Journal, 2016
Background: MicroRNAs (miRNAs) are innovative and informative blood-based biomarkers involved in numerous pathophysiological processes. In this study and based on our previous experimental data, we investigated miR-126, miR-143, miR-145, miR-155 and miR-223 as potential circulating biomarkers for the diagnosis and prognosis of patients with chronic kidney disease (CKD). The primary objective of this study was to assess the levels of miRNA expression at various stages of CKD. Methods: RNA was extracted from serum, and RT-qPCR was performed for the five miRNAs and cel-miR-39 (internal control). Results: Serum levels of miR-143,-145 and-223 were elevated in patients with CKD compared with healthy controls. They were further increased in chronic haemodialysis patients, but were below control levels in renal transplant recipients. In contrast, circulating levels of miR-126 and miR-155 levels, which were also elevated in CKD patients, were lower in the haemodialysis group and even lower in the transplant group. Four of the five miRNA species were correlated with estimated glomerular filtration rate, and three were correlated with circulating uraemic toxins. Conclusions: This exploratory study suggests that specific miRNAs could be biomarkers for complications of CKD, justifying further studies to link changes of miRNA levels with outcomes in CKD patients.
Review: The role of microRNAs in kidney disease
Nephrology, 2010
This is a comprehensive and scholarly review of the current knowledge of microRNAs (miRNAs) in renal disease. MiRNAs are emerging as important regulators of disease processes. Understanding how miRNAs modulate pathogenetic pathways is important, as therapeutic manipulation of miRNAs may evolve as a potential strategy for treating renal diseases in the future.
MicroRNAs in Kidney Disease: An Emerging Understanding
American Journal of Kidney Diseases, 2013
MicroRNAs (miRNAs) are short noncoding RNA molecules that function by negatively regulating the expression of their target genes in a tightly controlled manner. Accumulating evidence, based in part on effects seen after miRNA overexpression and/or knockdown, points to the critical involvement of miRNAs in kidney function in health and disease. In this review, we provide a quick overview of the biogenesis of miRNAs and their potential involvement in kidney development and normal function. We also discuss the current literature that has begun to uncover the role of miRNAs in the pathogenesis of kidney diseases, including diabetic nephropathy, hypertension, glomerulonephritis, and cancer. As such, miRNAs have potential utility in the clinical realm as disease biomarkers. Moreover, miRNAs represent an attractive therapeutic target for a number of kidney diseases. We close by discussing a number of potential challenges that face the field of miRNA research and clinical use.
2021
Besides conventional kidney diseases diagnostics, micro RNAs (miRNAs) assessment in urine and serum is considered to be a promising non-invasive method of diagnostics of renal parenchymal diseases and valuable therapeutic target also. The purpose of the study was to investigate the role of several miRNAs as a markers of kidney damage. Assessment of 45 chronic kidney disease (CKD) patients stage 1–4 and 17 healthy control. Sample of urine and blood was taken from each participant for molecular analysis using Real Time PCR method to identify such micro-RNAs as: hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-200a-5p, hsa-miR-29a-5p, hsa-miR-21-5p, hsa-miR-93-5p, and hsa-miR-196a-5p. Basic biochemical test was done. Analysis was performed in CKD patients group and subgroup with chronic glomerulonephritis (CGN) confirmed by kidney biopsy. Moreover, analysis was performed in subgroup with different estimated glomerular filtration rate (eGFR) (according to CKD–EPI equation: eGFR < 60 ml/min, e...
MicroRNA and nephropathy: emerging concepts
International Journal of Nephrology and Renovascular Disease, 2013
Micro ribonucleic acids (miRNAs) are short noncoding RNAs that inhibit gene expression through the post-transcriptional repression of their target mRNAs. Increasing evidence shows that miRNAs have emerged as key players in diverse biologic processes. Aberrant miRNA expression is also closely related to various human diseases, including kidney diseases. From clinical and experimental animal studies, emerging evidence demonstrates a critical role for miRNAs in renal pathophysiology. Renal fibrosis is the hallmark of various chronic kidney diseases and transforming growth factor beta (TGF-β) is recognized as a vital mediator of renal fibrosis because it can induce production of extracellular matrix proteins resulting in dysfunction of the kidneys. The relationship between TGF-β signaling and miRNAs expression during renal diseases has been recently established. TGF-β positively or negatively regulates expression of several miRNAs, such as miR-21, miR-192, miR-200, and miR-29. Both miR-192 and miR-21 are positively regulated by TGF-β1/Smad3 signaling and play a pathological role in kidney diseases. Conversely, members of both miR-29 and miR-200 families are negatively regulated by TGF-β/Smad3 and play a protective role in renal fibrosis by inhibiting the deposition of extracellular matrix and preventing epithelial-to-mesenchymal transition, respectively. Clinically, levels of miRNAs in circulation and urine may be potential biomarkers for detecting early stages of renal diseases and targeting miRNAs also provides promising therapeutic effects in rodent models of chronic kidney disease. However, mechanisms and roles of miRNAs under disease conditions remain to be explored. Thus, understanding the function of miRNAs in the pathogenesis of kidney diseases may offer an innovative approach for both early diagnosis and treatment of renal diseases.
MicroRNAs and Their Role in Progressive Kidney Diseases
Clinical Journal of the American Society of Nephrology, 2009
MicroRNAs (miRs) are a family of short non-coding RNAs. These endogenously produced factors have been shown to play important roles in gene regulation. The discovery of miRs has greatly expanded our knowledge of gene regulation at the posttranscriptional level. miRs inhibit target gene expression by blocking protein translation or by inducing mRNA degradation and therefore have the potential to modulate physiologic and pathologic processes. The imperative need to determine their cellular targets and disease relevance has sparked an unprecedented explosion of research in the miR field. Recent findings have revealed critical functions for specific miRs in cellular events such as proliferation, differentiation, development, and immune responses and in the regulation of genes relevant to human diseases. Of particular interest to renal researchers are recent reports that key miRs are highly expressed in the kidney and can act as effectors of TGF- actions and high glucose in diabetic kidney disease. Moreover, podocyte-specific deletion of Dicer, a key enzyme involved in miR biogenesis, led to proteinuria and severe renal dysfunction in mice. Hence, studies aimed at determining the in vitro and in vivo functions of miRs in the kidney could determine their value as therapeutic targets for progressive renal glomerular and tubular diseases. Translational approaches could be facilitated by the development of effective inhibitors of specific miRs and methods for optimal delivery of anti-miRs to the kidney. The major goal of this review is to highlight key functions of these miRs and their relationships to human diseases, with special emphasis on diabetic kidney disease.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/f5M4-ruLFPo Purpose: Currently available markers for early detection of diabetic nephropathy (DN), the leading cause of end stage renal disease, have some limitations. There is insufficient evidence from previous studies about the role of several circulating microRNAs (miRNAs) in the early development of DN. This study aimed to describe the expression of miRNA-377, miRNA-93, miRNA-25, miRNA-216a, and miRNA-21 in a sample of type 1 diabetic children and adolescents to explore their association with DN and some indices of kidney injury. Patients and Methods: Seventy type 1 diabetic patients, with 5 years' duration of diabetes or more, were recruited from Children's Hospital, Faculty of Medicine, Cairo University. Quantitative real-time reverse-transcription PCR (qRT-PCR) was used to measure the expression of the above mentioned miRNAs in serum and to assess its association with DN, and the studied risk factors. Results: There was a significantly higher percentage of up-regulation of miRNA-377 and miRNA-93 (P=0.03, 0.02, respectively) in addition to significant down-regulation of miRNA-25 (P=0.01) in patients with DN than in patients without DN. In patients with DN, expression of miR-216a was significantly negatively correlated with creatinine (r=−0.4, P=0.04) and positively correlated with eGFR using creatinine (r=0.5, P=0.03). In the same group, expression of miR-21 was positively correlated with urinary cystatin C (r=0.6, P=0.01) and was negatively correlated with e-GFR using cystatin c (r=−0.6, P=0.01). miRNA-93 was associated with increased risk (odds ratio=15, 95% CI=12.03-24.63, P=0.01), while miRNA-25 was associated with decreased risk for albuminuria (odds ratio=0.15, 95% CI=0.08-0.55, P=0.03). Conclusion: miRNA-377, miRNA-93, miRNA-216a, and miRNA-21 may be implicated in the pathogenesis of DN, while miRNA-25 may have a reno-protective role. More studies are needed to document the value of these miRNAs as diagnostic biomarkers as well as therapeutic targets in DN.
The expanding roles of microRNAs in kidney pathophysiology
Nephrology Dialysis Transplantation, 2018
MicroRNAs (miRNAs) are short single-stranded RNAs that control gene expression through base pairing with regions within the 3 0-untranslated region of target mRNAs. These small non-coding RNAs are now increasingly known to be involved in kidney physiopathology. In this review we will describe how miRNAs were in recent years implicated in cellular and animal models of kidney disease but also in chronic kidney disease, haemodialysed and grafted patients, acute kidney injury patients and so on. At the moment miRNAs are considered as potential biomarkers in nephrology, but larger cohorts as well as the standardization of methods of measurement will be needed to confirm their usefulness. It will further be of the utmost importance to select specific tissues and biofluids to make miRNAs appropriate in day-today clinical practice. In addition, up-or down-regulating miRNAs that were described as deregulated in kidney diseases may represent innovative therapeutic methods to cure these disorders. We will enumerate in this review the most recent methods that can be used to deliver miRNAs in a specific and suitable way in kidney and other organs damaged by kidney failure, such as the cardiovascular system.