title: Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls.
abstract: BACKGROUND
  Tubular atrophy and interstitial fibrosis mark the final stage in most forms of progressive kidney diseases. Little is known regarding changes in the tubular proteome. In this study, we investigated changes in the tubular proteome of normal or minimally damaged tubular tissue in the non-clipped kidney from rats with two-kidney one-clip (2K1C) hypertension.
  
  
  METHODS
  Formalin-fixed paraffin-embedded kidney sections from four 2K1C rats with hypertensive kidney damage and 6 sham rats were used. Tubulointerstitial tissue without discernable interstitial expansion or pronounced tubular alterations was microdissected and this was assumed to represent an early stage of chronic tubular damage in 2K1C. Samples were analyzed by mass spectrometry and relative protein abundances were compared between 2K1C and sham.
  
  
  RESULTS
  A total of 1,160 proteins were identified with at least 2 unique peptides, allowing for relative quantitation between samples. Among these, 151 proteins were more abundant, and 192 proteins were less abundant in 2K1C compared with sham. Transgelin, vimentin and creatine kinase B-type were among the proteins that were most increased in 2K1C. Ingenuity Pathway Analysis showed increased abundance of proteins related to Rho signaling and protein turnover (eIF2 signaling and protein ubiquitination), and decreased abundance of proteins related to fatty acid β-oxidation.
  
  
  CONCLUSIONS
  Tubular tissue from normal or minimally damaged hypertensive kidney damage demonstrate extensive proteomic changes with upregulation of pathways associated with progressive kidney damage, such as Rho signaling and protein turnover. Thus, proteomics presents itself to be a promising tool for the discovery of early damage markers from not yet morphologically visible tubular damage.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Finne
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Marti
authors.forename: Sabine
authors.initials: S
authors.lastname: Leh
authors.forename: Trude
authors.initials: T
authors.lastname: Skogstrand
authors.forename: Heidrun
authors.initials: H
authors.lastname: Vethe
authors.forename: Olav
authors.initials: O
authors.lastname: Tenstad
authors.forename: Frode S
authors.initials: FS
authors.lastname: Berven
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherer
authors.forename: Bjørn Egil
authors.initials: BE
authors.lastname: Vikse
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006978:Hypertension, Renovascular / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D009929:Organ Size; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation