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

Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of glomerular filtration barrier.
Am J Physiol Renal Physiol. 2020 May 11;:
Authors: Uchio-Yamada K, Yasuda K, Monobe Y, Akagi KI, Suzuki O, Manabe N
Abstract
Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies revealed that Tns2-deficient mice exhibited 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 remain unidentified. Here, we aimed to determine the role of Tns2 using newborn Tns2-deficient mice and murine primary podocytes. Ultrastructural analysis revealed that the developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin α2 accumulation, followed by GBM thickening. In addition, the analysis of primary podocytes revealed that Tns2 deficiency led to impaired podocyte-GBM interaction and massive expression of laminin α2 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 the stressed podocytes ectopically producing laminin α2, which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular...

Source: American Journal of Physiology. Renal Physiology - May 10, 2020 Category: Physiology Authors: Uchio-Yamada K, Yasuda K, Monobe Y, Akagi KI, Suzuki O, Manabe N Tags: Am J Physiol Renal Physiol Source Type: research