Vinculin is required to maintain glomerular barrier integrity
| Autor: | Lausecker, Franziska, Tian, Xuefei, Inoue, Kazunori, Wang, Zhen, Pedigo, Christopher E, Hassan, Hossam, Liu, Chang, Zimmer, Margaret, Jinno, Stephanie, Huckle, Abby L, Hamidi, Hellyeh, Ross, Robert S, Zent, Roy, Ballestrem, Christoph, Lennon, Rachel, Ishibe, Shuta |
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| Rok vydání: | 2018 |
| Předmět: |
Kidney Disease
podocyte Lipoid Mechanotransduction 1.1 Normal biological development and functioning Cells Knockout Clinical Sciences Renal and urogenital glomerular disease macromolecular substances Inbred C57BL Membranous Glomerulonephritis Membranous Mechanotransduction Cellular Article Focal Segmental Mice Glomerulonephritis Glomerulosclerosis Underpinning research Cell Movement 2.1 Biological and endogenous factors Animals Albuminuria Aetiology Phosphorylation Cells Cultured Mice Knockout Focal Adhesions Cultured Glomerulosclerosis Focal Segmental Podocytes vinculin Nephrosis Lipoid cell adhesion Urology & Nephrology Mice Inbred C57BL glomerular filtration barrier Focal Adhesion Kinase 1 Zonula Occludens-1 Protein Nephrosis Cell Surface Extensions Cellular |
| Zdroj: | Kidney international, vol 93, iss 3 Kidney International Lausecker, F, Tian, X, Inoue, K, Wang, Z, Pedigo, C E, Hassan, H, Liu, C, Zimmer, M, Jinno, S, Huckle, A L, Hamidi, H, Ross, R S, Zent, R, Ballestrem, C, Lennon, R & Ishibe, S 2017, ' Vinculin is required to maintain glomerular barrier integrity ', Kidney International . https://doi.org/10.1016/j.kint.2017.09.021 |
| Popis: | 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 invivo. 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. |
| Databáze: | OpenAIRE |
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