title: Novel approach for the detection of tubular cell migration into the interstitium during renal fibrosis in rats.
abstract: BACKGROUND
  The process of epithelial-mesenchymal transition (EMT), which is generally defined by phenotypic changes of injured tubules such as loss of epithelial markers or acquisition of mesenchymal markers, implies various activating steps, including proliferation, migration, and ability to produce extracellular matrix proteins. We established here a novel approach for the detection of tubular cell migration into the interstitium during renal fibrosis in vivo.
  
  
  RESULTS
  Using an osmotic pump, bromodeoxyuridine (BrdU) was continuously given to 7-week-old Wistar rats for 4 weeks, and BrdU-positive cells were detected by immunostaining. BrdU-positive cells were present in aquaporin-1-positive proximal tubules, but not in the interstitium of BrdU-treated rat kidneys. After unilateral ureteral obstruction (UUO), some BrdU-positive tubular cells protruded from the basement membrane and migrated into the interstitium. Interstitial BrdU-positive cells were co-localized with alpha-smooth muscle actin, fibroblast specific protein-1, vimentin, and type I collagen, but not with CD68 or CD3. No BrdU-positive cells were observed in the interstitium of sham-operated kidneys. The number of BrdU-positive cells migrating into the interstitium significantly increased and peaked at 8 days after UUO.
  
  
  CONCLUSIONS
  Long-term BrdU labeling marked some of the proximal tubular cells and enabled us to detect tubular cell migration into the interstitium after UUO. This simple method might be useful to detect EMT in vivo.
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nakasatomi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Maeshima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ikeuchi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sakairi
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, 371-8511 Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima