title: Identification of common and differential mechanisms of glomerulus and tubule senescence in 24-month-old rats by quantitative LC-MS/MS.
abstract: Kidney aging together with related renal disease had become a major clinical problem. Understanding the mechanisms of aging was important for suspending senescence and decreasing the incidence of aging-related diseases. In the present work, 24-month-old F344 rats were used as aging rats and 3-month-old rats were used as young controls. Senescence-associated-β-galactosidase staining results showed that the degree of senescence in renal tubules was more severe than that in glomeruli. We performed quantitative LC-MS to assess the differential protein expression profiles of senescent glomeruli and tubules. Bioinformatics analysis showed that aging, response to oxidative stress, nucleotide metabolism, amine acid metabolism, and inflammatory response were common mechanisms of glomerulus and tubule senescence. Differentially expressed proteins network mediated Golgi vesicle transport, actin filament based process, and regulation of cell death were associated with tubule senescence. More importantly, we found that the changes of four and a half LIM protein 2 (FHL2) were opposite in senescent glomeruli and tubules, and FHL2 could regulate p16 by suppressing T-box 3, which was involved in regulation of senescence in glomeruli and tubules. In conclusion, we assessed the mechanisms of senescence in aging glomeruli and tubules, and the results yielded new insight into kidney senescence.
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, P.R. China.|Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, P.R. China. lvyang1978@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, P.R. China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, P.R. China.
authors.forename: Haiteng
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, P.R. China. xmchen301@126.com.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000375:Aging; D000818:Animals; D002460:Cell Line; D016922:Cellular Senescence; D002853:Chromatography, Liquid; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D007684:Kidney Tubules / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D060850:LIM-Homeodomain Proteins / Q000032:analysis / Q000378:metabolism; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism; D018384:Oxidative Stress; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D011916:Rats, Inbred F344; D020825:T-Box Domain Proteins / Q000032:analysis / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C491381:Fhl2 protein, rat; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D020543:Proteome; D020825:T-Box Domain Proteins; D014157:Transcription Factors
keywords: Aging; Animal proteomics; FHL2; Glomerular; Tubule