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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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 Nephrology – Springer Journals

Published: May 28, 2018

References

  • The burden of chronic kidney disease: is rising rapidly worldwide
    Hamer, RA; Nahas, AM
  • CKD and infectious diseases in Asia Pacific: challenges and opportunities
    Jha, V; Prasad, N
  • Chronic kidney disease: global dimension and perspectives
    Jha, V; Garcia-Garcia, G; Iseki, K; Li, Z; Naicker, S; Plattner, B
  • CKD in Central America: a hot issue
    Brooks, DR; Ramirez-Rubio, O; Amador, JJ
  • End-stage renal disease in the El-Minia Governorate, upper Egypt: an epidemiological study
    Minshawy, O
  • Chronic kidney disease in two coastal districts of Andhra Pradesh, India: role of drinking water
    Reddy, DV; Gunasekar, A
  • Medical geology in tropical countries with special reference to Sri Lanka
    Dissanayake, CB; Chandrajith, R
  • Cyanobacteria and cyanotoxins in well waters of the girandurukotte, ckdu endemic area in Sri Lanka; do they drink safe water?
    Liyanage, M; Magana-arachchi, D; Priyadarshika, C; Abeysekara, T; Guneratne, L
  • Chronic kidney disease of unknown aetiology and ground-water ionicity: study based on Sri Lanka
    Dharma-Wardana, MW; Amarasiri, SL; Dharmawardene, N; Panabokke, CR
  • Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country
    Jayatilake, N; Mendis, S; Maheepala, P; Mehta, FR; Team, CKNRP
  • Drinking water quality and chronic kidney disease of unknown etiology (CKDu): synergic effects of fluoride, cadmium and hardness of water
    Wasana, HM; Aluthpatabendi, D; Kularatne, WM; Wijekoon, P; Weerasooriya, R; Bandara, J
  • Global dimensions of chronic kidney disease of unknown etiology (CKDu): a modern era environmental and/or occupational nephropathy?
    Weaver, VM; Fadrowski, JJ; Jaar, BG
  • Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka
    Nanayakkara, S; Senevirathna, ST; Parahitiyawa, NB; Abeysekera, T; Chandrajith, R; Ratnatunga, N
  • An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka
    Nanayakkara, S; Senevirathna, ST; Abeysekera, T; Chandrajith, R; Ratnatunga, N; Gunarathne, ED
  • Upregulation of oxidative stress related genes in a chronic kidney disease attributed to specific geographical locations of Sri Lanka
    Sayanthooran, S; Magana-Arachchi, DN; Gunerathne, L; Abeysekera, TDJ; Sooriyapathirana, SS
  • Serological evidence of hantavirus infection in Girandurukotte, an area endemic for chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka
    Gamage, CD; Yoshimatsu, K; Sarathkumara, YD; Kulendiran, T; Nanayakkara, N; Arikawa, J
  • Environmental health risk for the chronic renal failure in Sri Lanka. 31st Congress on Science and Technology of Thailand
  • Chronic renal failure among farm families in cascade irrigation systems in Sri Lanka associated with elevated dietary cadmium levels in rice and freshwater fish (Tilapia)
    Bandara, JM; Senevirathna, DM; Dasanayake, DM; Herath, V; Bandara, JM; Abeysekara, T
  • WHO water quality standards Vs Synergic effect(s) of fluoride, heavy metals and hardness in drinking water on kidney tissues
    Wasana, HM; Perera, GD; Gunawardena, PS; Fernando, PS; Bandara, J
  • Uncertain etiologies of proteinuric-chronic kidney disease in rural Sri Lanka
    Athuraliya, NT; Abeysekera, TD; Amerasinghe, PH; Kumarasiri, R; Bandara, P; Karunaratne, U
  • Arterial stiffness & Sri Lankan chronic kidney disease of unknown origin
    Gifford, F; Kimmitt, R; Herath, C; Webb, DJ; Melville, V; Siribaddana, S
  • Genomic expression profiling of human inflammatory cardiomyopathy (DCMi) suggests novel therapeutic targets
    Wittchen, F; Suckau, L; Witt, H; Skurk, C; Lassner, D; Fechner, H
  • Repeated observation of breast tumor subtypes in independent gene expression data sets
    Sorlie, T; Tibshirani, R; Parker, J; Hastie, T; Marron, JS; Nobel, A
  • beadarray: R classes and methods for Illumina bead-based data
    Dunning, MJ; Smith, ML; Ritchie, ME; Tavare, S
  • Orchestrating high-throughput genomic analysis with bioconductor
    Huber, W; Carey, VJ; Gentleman, R; Anders, S
  • Complex heatmaps reveal patterns and correlations in multidimensional genomic data
    Gu, Z; Eils, R; Schlesner, M
  • Adjusting batch effects in microarray expression data using Empirical Bayes methods
    Johnson, WE; Rabinovic, A; Li, C
  • Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method
    Livak, KJ; Schmittgen, TD
  • Molecular cell biology
    Lodish, H; Berk, A; Zipursky, SL; Matsudaira, P; Baltimore, D; Darnell, J
  • Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka
    Nanayakkara, S; Komiya, T; Ratnatunga, N; Senevirathna, ST; Harada, KH; Hitomi, T
  • Fundamentals of renal pathology
    Fogo, AB; Cohen, HC; Colvin, RB; Jennette, JC; Alpers, CE
  • Renal interstitial fibrosis: mechanisms and evaluation in: current opinion in nephrology and hypertension
    Farris, AB; Colvin, RB
  • How cells respond to interferons
    Stark, GR; Kerr, IM; Williams, BR; Silverman, RH; Schreiber, RD
  • Interferon-stimulated genes and their antiviral effector functions
    Schoggins, JW; Rice, CM
  • Interferon-stimulated genes: a complex web of host defenses
    Schneider, WM; Chevillotte, MD; Rice, CM
  • Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays
    Der, SD; Zhou, A; Williams, BRG; Silverman, RH
  • Direct effects of type I interferons on cells of the immune system
    Hervas-Stubbs, S; Perez-Gracia, JL; Rouzaut, A; Sanmamed, MF; Bon, A; Melero, I
  • Chronic kidney disease in the developing world
    Barsoum, RS
  • Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion
    Shrestha, N; Bahnan, W; Wiley, DJ; Barber, G; Fields, KA; Schesser, K
  • Inhibition of host translation by virus infection in vivo
    Toribio, R; Ventoso, I
  • Fluoride-induced autophagy via the regulation of phosphorylation of mammalian targets of rapamycin in mice leydig cells
    Zhang, J; Zhu, Y; Shi, Y; Han, Y; Liang, C; Feng, Z
  • Roles of EGFR, PI3K, AKT, and mTOR in heavy metal-induced cancer
    Carpenter, RL; Jiang, BH
  • Zika virus NS4A and NS4B proteins deregulate Akt-mTOR signaling in human fetal neural stem cells to inhibit neurogenesis and induce autophagy
    Liang, Q; Luo, Z; Zeng, J; Chen, W; Foo, S-S; Lee, S-A
  • The TORrid affairs of viruses: effects of mammalian DNA viruses on the PI3K-Akt-mTOR signalling pathway
    Buchkovich, NJ; Yu, Y; Zampieri, CA; Alwine, JC
  • Excellent diagnostic characteristics for ultrafast gene profiling of DEFA1-IL1B-LTF in detection of prosthetic joint infections
    Fillerova, R; Gallo, J; Radvansky, M; Kraiczova, V; Kudelka, M; Kriegova, E
  • Cell death and cytokine production induced by cadmium in leukocytes of cord blood and peripheral blood of adults
    Kamińska, T; Tustanowska-Stachura, A; Słotwińska, M; Szuster-Ciesielska, A; Stasiak, M; Kandefer-Szerszeń, M
  • Fluoride augments the mitogenic and antigenic response of human blood lymphocytes in vitro
    Loftenius, A; Andersson, B; Butler, J; Ekstrand, J
  • Sodium fluoride induces podosome formation in endothelial cells
    Tatin, F; Grise, F; Reuzeau, E; Genot, E; Moreau, V
  • Research issues in aluminium toxicity: proceedings of the workshop on research issues in aluminium toxicity. International symposium on aluminium toxicity, 1995
  • Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride
    Agalakova, NI; Gusev, GP
  • Co-occurrence of arsenic and fluoride in groundwater of semi-arid regions in Latin America: genesis, mobility and remediation
    Alarcon-Herrera, MT; Bundschuh, J; Nath, B; Nicolli, HB; Gutierrez, M; Reyes-Gomez, VM
  • A concurrent exposure to arsenic and fluoride from drinking water in Chihuahua, Mexico
    González-Horta, C; Ballinas-Casarrubias, L; Sánchez-Ramírez, B; Ishida, MC; Barrera-Hernández, A; Gutiérrez-Torres, D
  • Relationship between drinking water fluoride levels, dental fluorosis, dental caries and associated risk factors in 9–12 years old school children of Nelakondapally Mandal of Khammam District, Andhra Pradesh, India: a cross-sectional survey
    Shanthi, M; Reddy, BV; Venkataramana, V; Gowrisankar, S; Reddy, BVT; Chennupati, S
  • Cellular mechanisms of cadmium-induced toxicity: a review
    Rani, A; Kumar, A; Lal, A; Pant, M
  • Overexpression of IFN-induced protein with tetratricopeptide repeats 3 (IFIT3) in pancreatic cancer: cellular “pseudoinflammation” contributing to an aggressive phenotype
    Niess, H; Camaj, P; Mair, R; Renner, A; Zhao, Y; Jackel, C
  • The role of IFITM3 in the growth and migration of human glioma cells
    Zhao, B; Wang, H; Zong, G; Li, P
  • Differential toxicogenomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin in malignant and nonmalignant human airway epithelial cells
    Martinez, JM; Afshari, CA; Bushel, PR; Masuda, A; Takahashi, T; Walker, NJ
  • Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
    Tang, K-F; Ren, H; Cao, J; Zeng, G-L; Xie, J; Chen, M
  • Distinct roles for Nod2 protein and autocrine interleukin-1beta in muramyl dipeptide-induced mitogen-activated protein kinase activation and cytokine secretion in human macrophages
    Hedl, M; Abraham, C
  • Expression of podocyteassociated molecules in acquired human kidney diseases
    Koop, K; Eikmans, M; Baelde, HJ; Kawachi, H; Heer, E; Paul, LC

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