The Proteasome Inhibitor, MG132, Attenuates Diabetic Nephropathy by Inhibiting SnoN Degradation In Vivo and In Vitro

Abstract EN

Transforming growth factor-β (TGF-β) has been shown to be involved in diabetic nephropathy (DN).

The SnoN protein can regulate TGF-β signaling through interaction with Smad proteins.

Recent studies have shown that SnoN is mainly degraded by the ubiquitin-proteasome pathway.

However, the role of SnoN in the regulation of TGF-β/Smad signaling in DN is still unclear.

In this study, diabetic rats were randomly divided into a diabetic control group (DC group) and a proteasome inhibitor (MG132) diabetes therapy group (DT group).

Kidney damage parameters and the expression of SnoN, Smurf2, and TGF-β were observed.

Simultaneously, we cultured rat glomerular mesangial cells (GMCs) stimulated with high glucose, and SnoN and Arkadia expression were measured.

Results demonstrated that 24-hour urine protein, ACR, BUN, and the expression of Smurf2 and TGF-β were significantly increased (P<0.05), whereas SnoN was significantly decreased in the DC group (P<0.05).

However, these changes diminished after treatment with MG132.

SnoN expression in GMCs decreased significantly (P<0.05), but Arkadia expression gradually increased due to high glucose stimulation (P<0.05), which could be almost completely reversed by MG132 (P<0.05).

The present results support the hypothesis that MG132 may alleviate kidney damage by inhibiting SnoN degradation and TGF-β activation, suggesting that the ubiquitin-proteasome pathway may become a new therapeutic target for DN.