title: Upregulation of nestin in proximal tubules may participate in cell migration during renal repair.
abstract: The characteristics of renal tubular progenitor/precursor cells and the role of renal tubule regeneration in the repair of remnant kidneys (RKs) after nephrectomy are not well known. In the present study of a murine model of subtotal nephrectomy, we used immunofluorescence (IF), immunoblot analysis, and in situ hybridization methods to demonstrate that nestin expression was transiently upregulated in tubule cells near the incision edges of RKs. The nestin-positive tubules were immature proximal tubules that colabeled with lotus tetragonolobus agglutinin but not with markers of mature tubules (aquaporin-1, Tamm-Horsfall protein, and aquaporin-2). In addition, many of the nestin-expressing tubule cells were actively proliferative cells, as indicated by colabeling with bromodeoxyuridine. Double-label IF and immunoblot analysis also showed that the upregulation of tubular nestin was associated with enhanced transforming growth factor-β1 (TGF-β1) expression in the incision edge of RKs but not α-smooth muscle actin, which is a marker of fibrosis. In cultured human kidney proximal tubule cells (HKC), immunoblot analysis indicated that TGF-β1 induced nestin expression and loss of E-cadherin expression, suggesting an association of nestin expression and cellular dedifferentiation. Knockdown of nestin expression by a short hairpin RNA-containing plasmid led to decreased migration of HKC cells that were induced by TGF-β1. Taken together, our results suggest that the tubule repair that occurs during the recovery process following nephrectomy may involve TGF-β1-induced nestin expression in immature renal proximal tubule cells and the promotion of renal cell migration.
authors.affiliation: Division of Nephrology, Huashan Hospital, Shanghai Medical College, Fudan Univ., Shanghai, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wen
authors.forename: Li
authors.initials: L
authors.lastname: Ni
authors.forename: Li
authors.initials: L
authors.lastname: You
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Chuan-Ming
authors.initials: CM
authors.lastname: Hao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000502:physiology* / Q000601:surgery; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009392:Nephrectomy; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D064231:Nestin; D034741:RNA, Small Interfering / Q000494:pharmacology; D012038:Regeneration / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1