title: α(E)-catenin regulates BMP-7 expression and migration in renal epithelial cells.
abstract: BACKGROUND
  The aging kidney has a decreased ability to repair following injury. We have shown a loss in expression of α-catenin in the aging rat kidney and hypothesize that decreased α-catenin expression in tubular epithelial cells results in diminished repair capacity.
  
  
  METHODS
  In an effort to elucidate alterations due to the loss of α-catenin, we generated NRK-52E cell lines with stable knockdown of α(E)-catenin.
  
  
  RESULTS
  α(E)-catenin knockdown resulted in decreased wound repair due to alterations in cell migration. Analysis of gene expression in the α(E)-catenin knockdown cells demonstrated almost a complete loss of bone morphogenetic protein-7 (BMP-7) expression that was associated with decreased phospho-Smad1/5/8 staining. However, addition of exogenous BMP-7 increased phospho-Smad1/5/8, suggesting that the BMP-7 pathway remained intact in C2 cells. Given the potential role of BMP-7 in repair, we investigated its role in wound repair. Inhibition of BMP-7 decreased repair in non-targeted control cells; conversely, exogenous BMP-7 restored repair in α(E)-catenin knockdown cells to control levels.
  
  
  CONCLUSIONS
  Taken together, the data suggests that the loss of α(E)-catenin expression and subsequent downregulation of BMP-7 is a mechanism underlying the altered migration of tubular epithelial cells that contributes to the inability of the aging kidney to repair following injury.
authors.affiliation: Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, Mo., USA.
authors.forename: LaNita A
authors.initials: LA
authors.lastname: Nichols
authors.forename: Anna
authors.initials: A
authors.lastname: Slusarz
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grunz-Borgmann
authors.forename: Alan R
authors.initials: AR
authors.lastname: Parrish
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D004847:Epithelial Cells / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007684:Kidney Tubules; D008297:Male; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D014945:Wound Healing; D051178:alpha Catenin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D055419:Bone Morphogenetic Protein 7; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D051178:alpha Catenin