title: Gene expression profile of renal proximal tubules regulated by proteinuria.
abstract: BACKGROUND
  Proximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis.
  
  
  METHODS
  Gene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria.
  
  
  RESULTS
  By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts.
  
  
  CONCLUSIONS
  The gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, School of Allied Health Sciences, and Institute for Molecular and Cellular Biology, Osaka University, Osaka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Masaru
authors.initials: M
authors.lastname: Takenaka
authors.forename: Jun-Ya
authors.initials: JY
authors.lastname: Kaimori
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nagasawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kosugi
authors.forename: Shouko
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Kousaku
authors.initials: K
authors.lastname: Okubo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D030161:Avian Proteins; D001483:Base Sequence; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008074:Lipoproteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009395:Nephritis, Interstitial / Q000235:genetics / Q000503:physiopathology; D011506:Proteins / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000950:Antigens, Ly; D030161:Avian Proteins; C466983:GS188 protein, mouse; C116062:LR8 protein, chicken; D008074:Lipoproteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C084839:thymic shared antigen-1