#3474 role of integrin, fibronectin, and upar in podocyte-glomerular basement membrane interaction under fluid shear stress

Abstract Background and Aims Podocyte-glomerular basement membrane (GBM) interaction is the main component to maintain glomerular filtration barrier. Interestingly, the podocyte-GBM interaction is not static, but dynamic according to various podocyte conditions. Thus, we hypothesized that the podocyte-GBM interaction would be changed under stress conditions such as fluid shear stress (FSS). Here, we aim to explore the change of specific integrin (Itg αVβ3), fibronectin, and uPAR in the podocyte-GBM interaction under fluid shear stress (FSS). Method We used conditionally immortalized human podocyte cells which were differentiated only under specific (non-permissive) temperature (37°C). We exposed the podocytes to 200 rpm of FSS and applied various dish coating agents. We observed cell morphology and documented the protein and mRNA expressions of Itg β3, fibronectin, and uPAR under FSS. Results Podocyte morphology became more elongated with actin rearrangement under FSS. Protein expression of Itg β3 did not change under FSS, while activated Itg β3 increased from early phase (30 min after exposure to FSS) (Figure 1). Fibronectin (Figure 2) and uPAR (Figure 3) gradually increased under FSS. mRNA expressions of Itg β3, fibronectin, and uPAR did not change under FSS. Cell viability increased in collagen-1 coated dish compared to non-coated under FSS. Conclusion This study demonstrates that Itg αVβ3 is activated, fibronectin and uPAR increase under FSS. In addition, it is shown that extracellula matrix contributes to podocyte stability. The results suggest that Itg αVβ3, fibronectin and uPAR may have specific roles to maintain podocyte's stability through the modulation of the podocyte-GBM interaction.