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Publication : Vinculin is required to maintain glomerular barrier integrity.

First Author  Lausecker F Year  2018
Journal  Kidney Int Volume  93
Issue  3 Pages  643-655
PubMed ID  29241625 Mgi Jnum  J:274838
Mgi Id  MGI:6296228 Doi  10.1016/j.kint.2017.09.021
Citation  Lausecker F, et al. (2018) Vinculin is required to maintain glomerular barrier integrity. Kidney Int 93(3):643-655
abstractText  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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