[Background]
Podocytes, a component of glomerular filtration barrier, are damaged under various stresses in kidney diseases. Previously, we revealed that a transcription factor old astrocyte specifically induced substance (OASIS) in kidney myofibroblasts promoted kidney fibrosis. However, the role of OASIS in podocytes remains unclear.
[Methods/Results]
LPS treatment increased OASIS expression in podocytes. To examine the roles of OASIS in podocytes, we generated podocyte-specific OASIS knockout (cKO) mice. Podocyte-specific OASIS deletion suppressed LPS-increased serum creatinine level, but did not influence albuminuria and podocyte injury. Interestingly, on the other hand, OASIS cKO mice were protected from LPS-mediated tubular injury. Microarray analysis using OASIS-overexpressed podocytes revealed that PRKCI was negatively regulated by OASIS in podocytes. We also found that recombinant PRKCI suppressed LPS-induced tubular injury in HK-2 cells in a dose-dependent manner. Finally, we established podocyte-restricted OASIS overexpressing transgenic mice and revealed that OASIS overexpression in podocytes caused tubular injury and kidney fibrosis, concomitant with severe albuminuria and podocyte foot process effacement.
[Conclusion]
Upregulation of OASIS in podocytes disturbs kidney homeostasis, leading to renal dysfunction.