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Transcriptome analysis supports viral infection and fluoride toxicity as contributors to chronic kidney disease of unknown etiology (CKDu) in Sri Lanka

Transcriptome analysis supports viral infection and fluoride toxicity as contributors to chronic... Purpose Chronic kidney disease of unknown etiology (CKDu), having epidemic characteristics, is being diagnosed increas- ingly in certain tropical regions of the world, mainly Latin America and Sri Lanka. They have been observed primarily in farming communities and current hypotheses point toward many environmental and occupational triggers. CKDu does not have common etiologies of chronic kidney disease (CKD) such as hypertension, diabetes, or autoimmune disease. We aimed to understand the molecular processes underlying CKDu in Sri Lanka using transcriptome analysis. Methods RNA extracted from whole blood was reverse transcribed and used for microarray analysis using the Human HT-12 v.4 array (Illumina). Pathway analysis was carried out using ingenuity pathway analysis (IPA—Qiagen). Microarray results were validated using real-time PCR of five selected genes. Results Pathways related to innate immune response, including interferon signaling, inflammasome signaling and TREM1 signaling had the most significant positive activation z scores, where as EIF2 signaling and mTOR signaling had the most significant negative activation z scores. Pathways previously linked to fluoride toxicity; G-protein activation, Cdc42 signaling, Rac signaling and RhoA signaling were activated in CKDu patients. The most significantly activated biological functions were cell death, cell movement and antimicrobial response. Significant toxicological functions were mitochondrial http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Urology and Nephrology Springer Journals

Transcriptome analysis supports viral infection and fluoride toxicity as contributors to chronic kidney disease of unknown etiology (CKDu) in Sri Lanka

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References (65)

Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer Science+Business Media B.V., part of Springer Nature
Subject
Medicine & Public Health; Nephrology; Urology
ISSN
0301-1623
eISSN
1573-2584
DOI
10.1007/s11255-018-1892-z
Publisher site
See Article on Publisher Site

Abstract

Purpose Chronic kidney disease of unknown etiology (CKDu), having epidemic characteristics, is being diagnosed increas- ingly in certain tropical regions of the world, mainly Latin America and Sri Lanka. They have been observed primarily in farming communities and current hypotheses point toward many environmental and occupational triggers. CKDu does not have common etiologies of chronic kidney disease (CKD) such as hypertension, diabetes, or autoimmune disease. We aimed to understand the molecular processes underlying CKDu in Sri Lanka using transcriptome analysis. Methods RNA extracted from whole blood was reverse transcribed and used for microarray analysis using the Human HT-12 v.4 array (Illumina). Pathway analysis was carried out using ingenuity pathway analysis (IPA—Qiagen). Microarray results were validated using real-time PCR of five selected genes. Results Pathways related to innate immune response, including interferon signaling, inflammasome signaling and TREM1 signaling had the most significant positive activation z scores, where as EIF2 signaling and mTOR signaling had the most significant negative activation z scores. Pathways previously linked to fluoride toxicity; G-protein activation, Cdc42 signaling, Rac signaling and RhoA signaling were activated in CKDu patients. The most significantly activated biological functions were cell death, cell movement and antimicrobial response. Significant toxicological functions were mitochondrial

Journal

International Urology and NephrologySpringer Journals

Published: May 28, 2018

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