Thrombospondin Type 1 Domain–Containing 7A Localizes to the Slit Diaphragm and Stabilizes Membrane Dynamics of Fully Differentiated Podocytes

作者：Johanna Herwig, Sinah Skuza, Wiebke Sachs, Marlies Sachs, Antonio Virgilio Failla, Gabriele M. Rune, Tobias Meyer, Lars Fester, Catherine Meyer‐Schwesinger · 发表于：Journal of the American Society of Nephrology · 年份：2019 · DOI：10.1681/asn.2018090941 · 被引用次数：70 · 研究领域：Renal Diseases and Glomerulopathies、Lymphatic System and Diseases、Lymphatic Disorders and Treatments

Significance Statement Among adults with membranous nephropathy, about 3%–5% have autoantibodies directed against thrombospondin type 1 domain–containing 7A (THSD7A), a podocyte-expressed transmembrane protein. To better understand the effects of THSD7A autoantibodies in this disease, the authors investigated THSD7A’s temporal expression, spatial expression, and biological function in podocytes. They found that embryonic THSD7A expression begins on glomerular vascularization and slit diaphragm formation and that THSD7A and THSD7A autoantibodies localize to the slit diaphragm domain of foot processes. Expression of THSD7A in cultured human podocytes was associated with enhanced adhesion and decreased ability to migrate, suggesting that THSD7A may be involved in stabilizing the slit diaphragm and that autoantibodies to THSD7A might structurally and functionally alter the slit diaphragm’s permeability to protein. Background About 3%–5% of adults with membranous nephropathy have autoantibodies directed against thrombospondin type 1 domain–containing 7A (THSD7A), a podocyte-expressed transmembrane protein. However, the temporal and spatial expression of THSD7A and its biologic function for podocytes are unknown, information that is needed to understand the effects of THSD7A autoantibodies in this disease. Methods Using a variety of microscopic techniques, we analyzed THSD7A localization in postnatal, adult, and autoantibody-injected mice as well as in human podocytes. We also anal...