Increase of integrin-linked kinase activity in cultured podocytes upon stimulation with plasma from patients with recurrent FSGS.
Recurrent focal segmental glomerulosclerosis (FSGS) is a major challenge in the field of transplantation. Integrin-linked kinase (ILK) has emerged as a key mediator of podocyte-glomerular basement membrane (GBM) interactions. To clarify the involvement of plasma factors in FSGS recurrence, we examined the effects of plasma from FSGS patients with or without posttransplant recurrence on cultured podocytes, focusing particularly on ILK activity. Podocytes from a conditionally immortalized mouse podocyte cell line were treated with plasma from 11 FSGS patients, and ILK activity was determined using an immune complex kinase assay. Treatment with plasma from three patients with recurrence induced an increase in ILK activity. In contrast, no increase in ILK activity was observed in cultured podocytes treated with plasma from the remaining three patients with recurrence and five patients without recurrence. Cultured podocytes treated with plasma that induced ILK activity showed alterations of focal contact and detachment from the laminin matrix. In conclusion, this preliminary study provides experimental evidence suggesting the possible presence of circulating toxic factors in the plasma of some patients with recurrent FSGS, which induce an increase in podocyte ILK activity that may lead to the detachment of podocytes from the GBM.
Department of Pediatric Nephrology, Tokyo Women's Medical University, School of Medicine, Tokyo, Japan. hattori@kc.twmu.ac.jp
M
M
Hattori
Y
Y
Akioka
H
H
Chikamoto
N
N
Kobayashi
K
K
Tsuchiya
M
M
Shimizu
S
S
Kagami
H
H
Tsukaguchi
D000293:Adolescent; D000818:Animals; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D010949:Plasma; D050199:Podocytes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D012008:Recurrence; D000099200:Scaffold Protein ILK
D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK