Idiopathic nephrotic syndrome (INS) is characterized by proteinuria, in which podocyte dysfunction associated with NF-κB-mediated inflammation plays an important role. The nuclear factor of activated T cells 5 (NFAT5) has been shown to enhance NF-κB activity. However, whether NFAT5 is associated with proteinuria remains uncharacterized. NFAT5 is upregulated in the glomeruli in lipopolysaccharide (LPS)-induced mouse nephrotic proteinuria, as well as in LPS-treated podocytes in vitro. In addition, NFAT5 depletion improves filtration barrier function of LPS-treated podocytes in vitro. Mechanistically, NFAT5 depletion suppresses NF-κB activation and downstream proinflammatory reaction in LPS-treated podocytes, and moreover, NF-κB inhibition improves filtration barrier function of LPS-treated podocytes, suggesting that the suppressed NF-κB activity at least partly accounts for NFAT5 depletion-improved filtration barrier function. Furthermore, in vivo, depletion of NFAT5 suppresses NF-κB activity and ameliorates nephrotic proteinuria in LPS-treated mice. These findings suggest a protective role of NFAT5 depletion against LPS-induced nephrotic proteinuria and relate it to the suppression of NF-κB activity.
Keywords: NF-κB; NFAT5; idiopathic nephrotic syndrome; lipopolysaccharide; nephrotic proteinuria.