RNA-Seq analysis reveals new evidence for inflammation-related changes in aged kidney

// Daeui Park 1,2,3 , Byoung-Chul Kim 1,2 , Chul-Hong Kim 4 , Yeon Ja Choi 1 , Hyoung Oh Jeong 1 , Mi Eun Kim 5 , Jun Sik Lee 5 , Min Hi Park 1 , Ki Wung Chung 1 , Dae Hyun Kim 1 , Jaewon Lee 1 , Dong-Soon Im 1 , Seokjoo Yoon 2,3 , Sunghoon Lee 6 , Byung Pal Yu 7 , Jong Bhak 6 and Hae Young Chung 1 1 Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea 2 Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea 3 Human and Environmental Toxicology, School of Engineering, University of Science and Technology, Daejeon, Korea 4 GenomicTree Inc., Yuseong-gu, Daejeon, Korea 5 Department of Biology, College of Natural Sciences, Chosun University, Gwangju, Korea 6 Personal Genomics Institute,Genome Research Foundation, Suwon, Korea 7 Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Correspondence to: Hae Young Chung, email: // Jong Bhak, email: // Keywords : aging; inflammation; RNA-Seq; differentially expressed genes; novel genes; alternative splicing, Gerotarget Received : October 05, 2015 Accepted : April 18, 2016 Published : May 03, 2016 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.