title: RNA-Seq analysis reveals new evidence for inflammation-related changes in aged kidney.
abstract: Age-related dysregulated inflammation plays an essential role as a major risk factor underlying the pathophysiological aging process. To better understand how inflammatory processes are related to aging at the molecular level, we sequenced the transcriptome of young and aged rat kidney using RNA-Seq to detect known genes, novel genes, and alternative splicing events that are differentially expressed. By comparing young (6 months of age) and old (25 months of age) rats, we detected 722 up-regulated genes and 111 down-regulated genes. In the aged rats, we found 32 novel genes and 107 alternatively spliced genes. Notably, 6.6% of the up-regulated genes were related to inflammation (P < 2.2 × 10-16, Fisher exact t-test); 15.6% were novel genes with functional protein domains (P = 1.4 × 10-5); and 6.5% were genes showing alternative splicing events (P = 3.3 × 10-4). Based on the results of pathway analysis, we detected the involvement of inflammation-related pathways such as cytokines (P = 4.4 × 10-16), which were found up-regulated in the aged rats. Furthermore, an up-regulated inflammatory gene analysis identified the involvement of transcription factors, such as STAT4, EGR1, and FOSL1, which regulate cancer as well as inflammation in aging processes. Thus, RNA changes in these pathways support their involvement in the pro-inflammatory status during aging. We propose that whole RNA-Seq is a useful tool to identify novel genes and alternative splicing events by documenting broadly implicated inflammation-related genes involved in aging processes.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.|Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea.|Human and Environmental Toxicology, School of Engineering, University of Science and Technology, Daejeon, Korea.
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.|Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea.
authors.forename: Byoung-Chul
authors.initials: BC
authors.lastname: Kim
authors.affiliation: GenomicTree Inc., Daejeon, Korea.
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jeong
authors.affiliation: Department of Biology, College of Natural Sciences, Chosun University, Gwangju, Korea.
authors.forename: Mi Eun
authors.initials: ME
authors.lastname: Kim
authors.affiliation: Department of Biology, College of Natural Sciences, Chosun University, Gwangju, Korea.
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Dong-Soon
authors.initials: DS
authors.lastname: Im
authors.affiliation: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea.|Human and Environmental Toxicology, School of Engineering, University of Science and Technology, Daejeon, Korea.
authors.forename: Seokjoo
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Personal Genomics Institute,Genome Research Foundation, Suwon, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.affiliation: Personal Genomics Institute,Genome Research Foundation, Suwon, Korea.
authors.forename: Jong
authors.initials: J
authors.lastname: Bhak
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017398:Alternative Splicing; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005240:Feasibility Studies; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050797:STAT4 Transcription Factor / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms; D059467:Transcriptome; D015854:Up-Regulation; D000099169:Fos-Related Antigen 1
chemical_list: D015415:Biomarkers; D051766:Early Growth Response Protein 1; D016760:Proto-Oncogene Proteins c-fos; D012313:RNA; D050797:STAT4 Transcription Factor; D000099169:Fos-Related Antigen 1; C486110:Egr1 protein, rat
keywords: Gerotarget; RNA-Seq; aging; alternative splicing; differentially expressed genes; inflammation; novel genes