Glomerular regeneration is delayed in nephritic alpha 8-integrin-deficient mice: contribution of alpha 8-integrin to the regulation of mesangial cell apoptosis.
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.
Hartner
Andrea
A
Hospital for Children and Adolescents, Erlangen, Germany.
Marek
Ines
I
Cordasic
Nada
N
Haas
Christian
C
Schocklmann
Harald
H
Hulsmann-Volkert
Gudrun
G
Plasa
Isabel
I
Rascher
Wolfgang
W
Hilgers
Karl F
KF
Amann
Kerstin
K
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
D003435:Crotalid Venoms; D016023:Integrins; D034741:RNA, Small Interfering; C094866:integrin alpha8beta1