Saravanabavan Sayanthooran1, Lishanthe Gunerathne2, Tilak D J Abeysekera3, Dhammika N Magana-Arachchi4. 1. Molecular Microbiology and Human Diseases, National Institute of Fundamental Studies, Kandy, 20000, Sri Lanka. 2. Renal Research Centre, District Hospital, Girandurukotte, 90750, Sri Lanka. 3. Centre for Education, Research and Training on Kidney Diseases (CERTKID), Faculty of Medicine, University of Peradeniya, Peradeniya, 20400, Sri Lanka. 4. Molecular Microbiology and Human Diseases, National Institute of Fundamental Studies, Kandy, 20000, Sri Lanka. cellbio@ifs.ac.lk.
Abstract
PURPOSE: Chronic kidney disease of unknown etiology (CKDu), having epidemic characteristics, is being diagnosed increasingly 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 dysfunction, oxidative stress and apoptosis. CONCLUSIONS: Based on the molecular pathway analysis in CKDu patients and review of literature, viral infections and fluoride toxicity appear to be contributing to the molecular mechanisms underlying CKDu.
PURPOSE:Chronic kidney disease of unknown etiology (CKDu), having epidemic characteristics, is being diagnosed increasingly 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 fluoridetoxicity; G-protein activation, Cdc42 signaling, Rac signaling and RhoA signaling were activated in CKDupatients. The most significantly activated biological functions were cell death, cell movement and antimicrobial response. Significant toxicological functions were mitochondrial dysfunction, oxidative stress and apoptosis. CONCLUSIONS: Based on the molecular pathway analysis in CKDupatients and review of literature, viral infections and fluoridetoxicity appear to be contributing to the molecular mechanisms underlying CKDu.
Authors: María Teresa Alarcón-Herrera; Jochen Bundschuh; Bibhash Nath; Hugo B Nicolli; Melida Gutierrez; Victor M Reyes-Gomez; Daniel Nuñez; Ignacio R Martín-Dominguez; Ondra Sracek Journal: J Hazard Mater Date: 2012-08-10 Impact factor: 10.588
Authors: Hewa M S Wasana; Gamage D R K Perera; Panduka De S Gunawardena; Palika S Fernando; Jayasundera Bandara Journal: Sci Rep Date: 2017-02-14 Impact factor: 4.379