Vinculin is required to maintain glomerular barrier integrity
#MMPMID29241625
Lausecker F
; Tian X
; Inoue K
; Wang Z
; Pedigo CE
; Hassan H
; Liu C
; Zimmer M
; Jinno S
; Huckle AL
; Hamidi H
; Ross RS
; Zent R
; Ballestrem C
; Lennon R
; Ishibe S
Kidney Int
2018[Mar]; 93
(3
): 643-655
PMID29241625
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Cell-matrix interactions and podocyte intercellular junctions are key for
maintaining the glomerular filtration barrier. Vinculin, a cytoplasmic protein,
couples actin filaments to integrin-mediated cell-matrix adhesions and to
cadherin-based intercellular junctions. Here, we examined the role of vinculin in
podocytes by the generation of a podocyte-specific knockout mouse. Mice lacking
podocyte vinculin had increased albuminuria and foot process effacement following
injury in vivo. Analysis of primary podocytes isolated from the mutant mice
revealed defects in cell protrusions, altered focal adhesion size and signaling,
as well as impaired cell migration. Furthermore, we found a marked
mislocalization of the intercellular junction protein zonula occludens-1. In
kidney sections from patients with focal segmental glomerulosclerosis, minimal
change disease and membranous nephropathy, we observed dramatic differences in
the expression levels and localization of vinculin. Thus, our results suggest
that vinculin is necessary to maintain the integrity of the glomerular filtration
barrier by modulating podocyte foot processes and stabilizing intercellular
junctions.
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