Chronic kidney disease: Biomarker diagnosis to therapeutic targets

2019 ◽  
Vol 499 ◽  
pp. 54-63 ◽  
Author(s):  
Yan-Ni Wang ◽  
Shi-Xing Ma ◽  
Yuan-Yuan Chen ◽  
Lin Chen ◽  
Bao-Li Liu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Therapeutic Targets ◽  
Disease Biomarker

scholarly journals A functional landscape of chronic kidney disease entities from public transcriptomic data

2018 ◽  
Author(s):  
Ferenc Tajti ◽  
Christoph Kuppe ◽  
Asier Antoranz ◽  
Mahmoud M. Ibrahim ◽  
Hyojin Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gene Expression Data ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Kidney Tissue ◽  
Therapeutic Targets ◽  
Expression Data ◽  
Disease Entities

AbstractTo develop efficient therapies and identify novel early biomarkers for chronic kidney disease an understanding of the molecular mechanisms orchestrating it is essential. We here set out to understand how differences in CKD origin are reflected in gene expression. To this end, we integrated publicly available human glomerular microarray gene expression data for nine kidney disease entities that account for a majority of CKD worldwide. We included data from five distinct studies and compared glomerular gene expression profiles to that of non-tumor parts of kidney cancer nephrectomy tissues. A major challenge was the integration of the data from different sources, platforms and conditions, that we mitigated with a bespoke stringent procedure. This allowed us to perform a global transcriptome-based delineation of different kidney disease entities, obtaining a landscape of their similarities and differences based on the genes that acquire a consistent differential expression between each kidney disease entity and nephrectomy tissue. Furthermore, we derived functional insights by inferring activity of signaling pathways and transcription factors from the collected gene expression data, and identified potential drug candidates based on expression signature matching. We validated representative findings by immunostaining in human kidney biopsies indicating e.g. that the transcription factor FOXM1 is significantly and specifically expressed in parietal epithelial cells in RPGN whereas not expressed in control kidney tissue. These results provide a foundation to comprehend the specific molecular mechanisms underlying different kidney disease entities, that can pave the way to identify biomarkers and potential therapeutic targets. To facilitate this, we provide our results as a free interactive web application: https://saezlab.shinyapps.io/ckd_landscape/.Translational StatementChronic kidney disease is a combination of entities with different etiologies. We integrate and analyse transcriptomics analysis of glomerular from different entities to dissect their different pathophysiology, what might help to identify novel entity-specific therapeutic targets.

Abstract 98: Chronic Kidney Disease-Associated Atherosclerosis is Attenuated by Dual Inhibition of microRNA-92a and microRNA-489

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Carrie Wiese ◽  
Zhi-Qi Xu ◽  
Youmin Zhang ◽  
Yan Guo ◽  
Jianyong Zhong ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Therapeutic Targets ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Aortic Endothelium ◽  
Stat3 Phosphorylation ◽  
Increased Risk ◽  
Novel Therapeutic

Chronic kidney disease (CKD) subjects have an increased risk of developing cardiovascular disease, namely atherosclerosis. Endothelial dysfunction and inflammation are linked to the development of these diseases and recent work has identified a number of microRNAs (miRNAs) involved in these pathologies. As such, endothelial miRNAs are potential novel therapeutic targets to prevent and treat atherosclerosis. This study identified elevated aortic endothelial miR-92a-3p and miR-489-3p levels in a mouse model of CKD-associated atherosclerosis, Apoe -/- mice with 5/6 nephrectomy. A combinatorial miRNA inhibition strategy resulted in the loss of both miR-92a-3p and miR-489-3p in the endothelium and significantly reduced the atherosclerotic lesion area by 33%. Total RNA sequencing of the aortic endothelium identified many altered genetic pathways and metabolic processes in response to in vivo miRNA loss-of-function, including inflammation, phospholipid metabolism, and protein degradation pathways. Results suggest that the reduction in atherosclerosis levels were not likely to be linked to alterations in plasma cholesterol levels or kidney function since these physiological parameters were not improved upon miRNA inhibition. Nevertheless, novel miRNA targets were identified to be significantly elevated in the aortic endothelium that may reduce inflammation leading to the improved physiological phenotype. Fam220a , a negative regulator of signal transducer and activator of transcription 3 (STAT3) phosphorylation, mRNA levels were significantly reduced in CKD-atherogenic mice compared to controls, but miRNA inhibition in vivo blocked the Fam220a repression. Moreover, gene reporter (luciferase) assays with site-directed mutagenesis confirmed FAM220A as a direct target of miR-92a-3p. Furthermore, FAM220A mRNA levels were repressed in human coronary artery endothelial cells (HCAEC) with miR-92a-3p over-expression, which resulted in increased phosphorylation of STAT3. Collectively, these results suggest that endothelial miR-92a-3p and miR-489-3p are novel therapeutic targets to treat CKD-associated atherosclerosis.

Colon may provide new therapeutic targets for treatment of chronic kidney disease with Chinese medicine

2013 ◽  
Vol 19 (2) ◽  
pp. 86-91 ◽  
Author(s):  
Chuan Zou ◽  
Zhao-yu Lu ◽  
Yu-chi Wu ◽  
Li-hong Yang ◽  
Guo-bin Su ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Chinese Medicine ◽  
Kidney Disease ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

scholarly journals The application of multi-omics and systems biology to identify therapeutic targets in chronic kidney disease

2015 ◽  
Vol 31 (12) ◽  
pp. 2003-2011 ◽  
Author(s):  
Katryna Cisek ◽  
Magdalena Krochmal ◽  
Julie Klein ◽  
Harald Mischak
Keyword(s):  
Chronic Kidney Disease ◽  
Systems Biology ◽  
Kidney Disease ◽  
Therapeutic Targets
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