Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier
- 1 June 2020
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Renal Physiology
- Vol. 318 (6), F1520-F1530
- https://doi.org/10.1152/ajprenal.00055.2020
Abstract
Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies have revealed that Tns2-deficient mice exhibit defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by Tns2 deficiency remains unidentified. Here, we aimed to determine the role of Tns2 using newborn Tns2-deficient mice and murine primary podocytes. Ultrastructural analysis revealed that developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin-alpha(2) accumulation followed by GBM thickening. In addition, analysis of primary podocytes revealed that Tns2 deficiency led to impaired podocyte-GBM interaction and massive expression of laminin-alpha(2) in podocytes. Our study suggests that weakened podocyte-GBM interaction due to Tns2 deficiency causes increased mechanical stress on podocytes by continuous daily filtration after birth, resulting in stressed podocytes ectopically producing laminin-alpha(2) , which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular filtration barrier.Funding Information
- Japan Society for the Promotion of Science (26830063)
This publication has 33 references indexed in Scilit:
- Tenc1-Deficient Mice Develop Glomerular Disease in a Strain-Specific MannerNephron Experimental Nephrology, 2013
- Deletion of Cd151 Results in a Strain-Dependent Glomerular Disease Due to Severe Alterations of the Glomerular Basement MembraneThe American Journal of Pathology, 2008
- Development of the renal glomerulus: good neighbors and good fencesDevelopment, 2008
- Role of Laminin Terminal Globular Domains in Basement Membrane AssemblyPublished by Elsevier BV ,2007
- Podocyte-Specific Deletion of Integrin-Linked Kinase Results in Severe Glomerular Basement Membrane Alterations and Progressive GlomerulosclerosisJournal of the American Society of Nephrology, 2006
- Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin α5 in the glomerular basement membraneThe Journal of cell biology, 2003
- Positionally Cloned Gene for a Novel Glomerular Protein—Nephrin—Is Mutated in Congenital Nephrotic SyndromeMolecular Cell, 1998
- Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome.Genes & Development, 1996
- Development of tubular and glomerular cells of the kidneyKidney International, 1992
- Evidence for splicing new basement membrane into old during glomerular development in newborn rat kidneys.The Journal of cell biology, 1986