title: Glomerular regeneration is delayed in nephritic alpha 8-integrin-deficient mice: contribution of alpha 8-integrin to the regulation of mesangial cell apoptosis.
abstract: OBJECTIVE
  alpha(8)beta(1)-Integrin is expressed in mesangial cells. In vitro studies suggest a role for alpha(8)-integrin in the regulation of cell proliferation and apoptosis. We tested the hypothesis that alpha(8)-integrin is essential for the healing process after mesangioproliferative glomerulonephritis.
  
  
  METHODS
  Mice homozygous for a deletion of the alpha(8)-integrin chain were compared with wild-type mice. To study glomerular healing, we used the habu toxin model of reversible mesangioproliferative glomerulonephritis. Animals received 6 mg/kg habu toxin intravenously; controls received saline only.
  
  
  RESULTS
  Early mesangiolysis occurred in wild-type and alpha(8)-integrin-deficient mice. However, mesangiolysis was no longer detectable after 7 days in wild types but persisted after 14 days in alpha(8)-integrin-deficient animals. Mesangial activation marker alpha-smooth muscle actin was detectable only at day 7 in wild-type mice but persisted until day 14 in alpha(8)-integrin-deficient mice. In wild types, glomerular cell proliferation and apoptosis peaked at day 7 and decreased thereafter but remained elevated in alpha(8)-integrin-deficient mice until day 28. In cultivated mesangial cells, alpha(8)-integrin expression was associated with increased cell survival.
  
  
  CONCLUSIONS
  Interactions between alpha(8)-integrin and the mesangial matrix may contribute to healing of glomerular injury by influencing cell proliferation and apoptosis.
authors.affiliation: Hospital for Children and Adolescents, Erlangen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
authors.forename: Ines
authors.initials: I
authors.lastname: Marek
authors.forename: Nada
authors.initials: N
authors.lastname: Cordasic
authors.forename: Christian
authors.initials: C
authors.lastname: Haas
authors.forename: Harald
authors.initials: H
authors.lastname: Schocklmann
authors.forename: Gudrun
authors.initials: G
authors.lastname: Hulsmann-Volkert
authors.forename: Isabel
authors.initials: I
authors.lastname: Plasa
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D003435:Crotalid Venoms; D015870:Gene Expression; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016023:Integrins / Q000235:genetics*; D007678:Kidney Glomerulus / Q000473:pathology / Q000502:physiology*; D008297:Male; D050527:Mesangial Cells / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D034741:RNA, Small Interfering / Q000494:pharmacology; D012038:Regeneration / Q000502:physiology*; D012720:Severity of Illness Index; D017841:Trimeresurus
chemical_list: D003435:Crotalid Venoms; D016023:Integrins; D034741:RNA, Small Interfering; C094866:integrin alpha8beta1