Podocyte foot process effacement in very early phase of passive Heymann nephritis is not a prerequisite for proteinuria.
BACKGROUND
Although foot process effacement is a characteristic alteration of podocytes in the proteinuric state, whether this is the cause or the result of proteinuria is not understood. We studied the morphology and molecular background of foot process effacement in relation to proteinuria, using the passive Heymann nephritis (PHN) model.


METHODS
Foot process effacement was evaluated by electron microscopy. C3 deposition and the expression of alpha 3-integrin, a major adhesion molecule of podocytes, and actin cytoskeleton were examined by immunofluorescent staining. alpha 3-Integrin was also evaluated by immunoelectron microscopy. Western blotting was performed to examine whether anti-Fx1A recognizes alpha 3 beta 1-integrin.


RESULTS
Foot process effacement accompanied by decreased expression of alpha 3-integrin was already observed from day 1 after the injection of anti-Fx1A, but albuminuria was not observed until day 5. Complement activation, a key pathogenesis in PHN, was estimated to occur from day 2 after the appearance of foot process effacement. The degree of foot process effacement had not changed before the onset of albuminuria, while after the onset of albuminuria it significantly deteriorated with increased expression of actin. By immunoelectron microscopy, alpha 3-integrin decreased exclusively at the site of deposits. Western blotting showed anti-Fx1A recognizing beta1-integrin.


CONCLUSIONS
These findings indicate that complement-independent foot process effacement related to decreased expression of alpha 3 beta 1-integrin in a very early phase of PHN is not a prerequisite for proteinuria, and the deterioration of foot process effacement related to actin reorganization after the onset of albuminuria might be a secondary response to proteinuria.
Nosaka
Hitonari
H
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. hnosaka@aol.com
Tamura
Yoshifuru
Y
Kojima
Kenichiro
K
Uchida
Shunya
S
Nagase
Mitsumasa
M
D000199:Actins / Q000032:analysis; D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D015433:Glomerulonephritis, Membranous / Q000209:etiology / Q000473:pathology*; D039422:Integrin alpha3 / Q000032:analysis; D019012:Integrin beta1 / Q000032:analysis; D008297:Male; D050199:Podocytes / Q000473:pathology*; D011507:Proteinuria / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep
D000199:Actins; D003176:Complement C3; D039422:Integrin alpha3; D019012:Integrin beta1