Inhibition of OASIS in podocytes suppressed diabetes-induced kidney dysfunction

Abstract

[Background] Diabetes is a major risk factor for chronic kidney disease (CKD). However, the mechanisms of diabetes-induced kidney injury remain to be fully elucidated. Here, we focused on old astrocyte specifically induced substance (OASIS), a transcriptional factor, because OASIS mRNA is increased in kidneys of CKD patients in the Nephroseq database. The aim is to determine the pathological roles of OASIS in diabetes-induced kidney injury.

[Methods/Results] C57BL/6J mice were injected with STZ to induce diabetes. Laser microdissection and immunoblotting revealed that OASIS was upregulated in glomeruli of STZ-treated mice. OASIS was detected in podocytes by immunohistochemical staining. To examine the roles of OASIS in podocytes, we generated podocyte-specific OASIS knockout mice (CKO). Mice were subjected to unilateral nephrectomy (UNx) before STZ injection to accelerate kidney injury. After UNx-STZ treatment, the level of serum creatinine (sCr) and the rate of kidney weight to body weight (Kw/Bw) got lower in CKO, compared with control (sCr (mg/dL): control; 0.85±0.11, CKO; 0.59±0.14, Kw/Bw (mg/g): control; 15.0±1.5, CKO;12.4±1.2, P<0.05, N=3-5).

[Conclusion] Podocyte OASIS could be a therapeutic target for the treatment of diabetic kidney disease.