scholarly journals Urinary microRNA in kidney disease: utility and roles

2019 ◽  
Vol 316 (5) ◽  
pp. F785-F793 ◽  
Author(s):  
In O. Sun ◽  
Lilach O. Lerman

MicroRNAs (miRNAs) are small, noncoding single-stranded RNA oligonucleotides that modulate physiological and pathological processes by modulating target gene expression. Many miRNAs display tissue-specific expression patterns, the dysregulation of which has been associated with various disease states, including kidney disease. Mounting evidence implicates miRNAs in various biological processes, such as cell proliferation and differentiation and cancer. Because miRNAs are relatively stable in tissue and biological fluids, particularly when carried by extracellular vesicles, changes in their levels may reflect the development of human disease. Urinary miRNAs originate from primary kidney and urinary tract cells, cells infiltrating the renal tissue and shed in the urine, or the systemic circulation. Although their validity as biomarkers for kidney disease has not been fully established, studies have been applying analysis of miRNAs in the urine in an attempt to detect and monitor acute and chronic renal diseases. Because appreciation of the significance of miRNAs in the renal field is on the rise, an understanding of miRNA pathways that regulate renal physiology and pathophysiology is becoming critically important. This review aims to summarize new data obtained in this field of research. It is hoped that new developments in the use of miRNAs as biomarkers and/or therapy will help manage and contain kidney disease in affected subjects.

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.


2018 ◽  
Vol 50 (8) ◽  
pp. 590-604 ◽  
Author(s):  
Katherine J. Perschbacher ◽  
Guorui Deng ◽  
Rory A. Fisher ◽  
Katherine N. Gibson-Corley ◽  
Mark K. Santillan ◽  
...  

G protein-coupled receptor signaling mechanisms are implicated in many aspects of cardiovascular control, and dysfunction of such signaling mechanisms is commonly associated with disease states. Investigators have identified a large number of regulator of G protein signaling (RGS) proteins that variously contribute to the modulation of intracellular second-messenger signaling kinetics. These many RGS proteins each interact with a specific set of second-messenger cascades and receptor types and exhibit tissue-specific expression patterns. Increasing evidence supports the contribution of RGS proteins, or their loss, in the pathogenesis of cardiovascular dysfunctions. This review summarizes the current understanding of the functional contributions of RGS proteins, particularly within the B/R4 family, in cardiovascular disorders of pregnancy including gestational hypertension, uterine artery dysfunction, and preeclampsia.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 330
Author(s):  
Georgia Mandolesi ◽  
Francesca Romana Rizzo ◽  
Sara Balletta ◽  
Mario Stampanoni Bassi ◽  
Luana Gilio ◽  
...  

The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation. Additionally, we found that the CSF let-7b-5p levels were significantly reduced in patients with the progressive MS compared to patients with relapsing-remitting MS and were negatively correlated with characteristic hallmark processes of the two phases of the disease. Indeed, in the non-progressive phase, let-7b-5p inversely associated with both central and peripheral inflammation; whereas, in progressive MS, the CSF levels of let-7b-5p negatively correlated with clinical disability at disease onset and after a follow-up period. Overall, our results uncovered, by the means of a multidisciplinary approach and multiple statistical analyses, a new possible pleiotropic action of let-7b-5p in MS, with potential utility as a biomarker of MS course.


Author(s):  
Jing Liu ◽  
Yong Liu ◽  
Feng Wang ◽  
Mingyu Liang

The field of microRNA research has evolved from studies aiming to gauge the importance of microRNAs to those focusing on understanding a subset of specific microRNAs that have emerged as potent regulators of molecular systems and pathophysiological conditions. In this article, we review the molecular features and regulation of miR-204 and the growing body of evidence for an important role of miR-204 in the regulation of cardiovascular and renal physiology and pathophysiological processes. miR-204 exhibits a highly tissue-specific expression pattern, and miR-204 abundance is regulated by several transcriptional and posttranscriptional mechanisms. Strong evidence supports a role for miR-204 in attenuating pulmonary arterial hypertension and hypertensive and diabetic renal injury while promoting hypertension and endothelial dysfunction in a wide range of model systems. miR-204 may influence these disease processes by targeting several biological pathways in a tissue-specific manner. miR-204 is dysregulated in patients with cardiovascular and renal diseases. The unequivocal functional roles and clear clinical relevance indicate that miR-204 is a high-value microRNA in cardiovascular and renal diseases.


2019 ◽  
Vol 116 (38) ◽  
pp. 19200-19208 ◽  
Author(s):  
Zixu Zhou ◽  
Qiuyang Wu ◽  
Zhangming Yan ◽  
Haizi Zheng ◽  
Chien-Ju Chen ◽  
...  

Extracellular RNAs (exRNAs) are present in human serum. It remains unclear to what extent these circulating exRNAs may reflect human physiologic and disease states. Here, we developed SILVER-seq (Small Input Liquid Volume Extracellular RNA Sequencing) to efficiently sequence both integral and fragmented exRNAs from a small droplet (5 μL to 7 μL) of liquid biopsy. We calibrated SILVER-seq in reference to other RNA sequencing methods based on milliliters of input serum and quantified droplet-to-droplet and donor-to-donor variations. We carried out SILVER-seq on more than 150 serum droplets from male and female donors ranging from 18 y to 48 y of age. SILVER-seq detected exRNAs from more than a quarter of the human genes, including small RNAs and fragments of mRNAs and long noncoding RNAs (lncRNAs). The detected exRNAs included those derived from genes with tissue (e.g., brain)-specific expression. The exRNA expression levels separated the male and female samples and were correlated with chronological age. Noncancer and breast cancer donors exhibited pronounced differences, whereas donors with or without cancer recurrence exhibited moderate differences in exRNA expression patterns. Even without using differentially expressed exRNAs as features, nearly all cancer and noncancer samples and a large portion of the recurrence and nonrecurrence samples could be correctly classified by exRNA expression values. These data suggest the potential of using exRNAs in a single droplet of serum for liquid biopsy-based diagnostics.


Development ◽  
1989 ◽  
Vol 106 (3) ◽  
pp. 465-471
Author(s):  
D.G. Wilkinson ◽  
S. Bhatt ◽  
R.P. Ryseck ◽  
R. Bravo

c-jun and junB are cellular genes related to the viral oncogene v-jun and encode members of the AP-1 transcription factor gene family. These genes have been implicated in the control of the G0/G1 transition in fibroblasts. Here, we have investigated the potential roles of c-jun and junB during fetal growth and organogenesis in the mouse by in situ hybridization analysis of their expression patterns. c-jun expression is detected throughout organogenesis, and transcripts are detected in many tissues, although in restricted cell populations within developing cartilage, gut and the central nervous system (CNS). In cartilage, c-jun expression is associated with rapidly proliferating perichondrial cells, but occurs in postmitotic motor neurones in the CNS. junB expression is initiated between 14.5 and 17.5 days of development, and is restricted to differentiating epidermal cells and endodermal gut epithelium. These data suggest that c-jun and junB have distinct, tissue-specific roles in cell proliferation and differentiation during fetal development.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Menno Pruijm ◽  
Lucie Hofmann ◽  
Bruno Vogt ◽  
Marie-Eve Muller ◽  
Maciej Piskunowicz ◽  
...  

Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD). In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system) or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.


2013 ◽  
Author(s):  
AL Bookout ◽  
Y Jeong ◽  
M Downes ◽  
RT Yu ◽  
RM Evans ◽  
...  

2018 ◽  
Author(s):  
Madushani Dharmarwardana ◽  
André F. Martins ◽  
Zhuo Chen ◽  
Philip M. Palacios ◽  
Chance M. Nowak ◽  
...  

Superoxide overproduction is known to occur in multiple disease states requiring critical care yet non-invasive detection of superoxide in deep tissue remains a challenge. Herein, we report a metal-free magnetic resonance imaging (MRI) and electron paramagnetic resonance (EPR) active contrast agent prepared by “click conjugating” paramagnetic organic radical contrast agents (ORCAs) to the surface of tobacco mosaic virus (TMV). While ORCAs are known to be reduced <i>in vivo</i> to an MRI/EPR silent state, their oxidation is facilitated specifically by reactive oxygen species—in particular superoxide—and are largely unaffected by peroxides and molecular oxygen. Unfortunately, single molecule ORCAs typically offer weak MRI contrast. In contrast, our data confirm that the macromolecular ORCA-TMV conjugates show marked enhancement for <i>T<sub>1</sub></i> contrast at low field (<3.0 T), and <i>T<sub>2</sub></i> contrast at high field (9.4 T). Additionally, we demonstrated that the unique topology of TMV allows for “quenchless fluorescent” bimodal probe for concurrent fluorescence and MRI/EPR imaging, which was made possible by exploiting the unique inner and outer surface of the TMV nanoparticle. <a>Finally, we show TMV-ORCAs do not respond to normal cellular respiration, minimizing the likelihood for background, yet still respond to enzymatically produced superoxide in complicated biological fluids like serum.</a>


2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.


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