Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier.

Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies have revealed that -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 deficiency remains unidentified. Here, we aimed to determine the role of Tns2 using newborn deficient mice and murine primary podocytes. Ultrastructural analysis revealed that developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin-α accumulation followed by GBM thickening. In addition, analysis of primary podocytes revealed that deficiency led to impaired podocyte-GBM interaction and massive expression of laminin-α in podocytes. Our study suggests that weakened podocyte-GBM interaction due to deficiency causes increased mechanical stress on podocytes by continuous daily filtration after birth, resulting in stressed podocytes ectopically producing laminin-α, which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular filtration barrier.