Tim-1 alleviates lupus nephritis-induced podocyte injury via regulating autophagy

Lupus nephritis (LN) is a complication of systemic lupus erythematosus (SLE) which seriously threatens the health of people. Tim-1 is known to be associated with the pathogenesis of SLE. However, the role of Tim-1 in LN is still unclear.

To explore the expression and the potential regulatory molecular mechanism of Tim-1 in LN-induced podocyte injury.

An in vivo model of LN was established to detect the expression of Tim-1, inflammatory cytokines and autophagy-related proteins. Podocytes were treated with immunoglobulin G (IgG) to establish the LN in vitro model and then treated with an autophagy inhibitor. RT-qPCR and western blot were performed to investigate the effect of Tim-1 on inflammatory responses as well as autophagy in podocytes. The function of Tim-1 in IgG-induced podocytes was detected by CCK-8 and flow cytometry, respectively.

Tim-1, L3BII/L3BI ratio and inflammatory cytokines were upregulated in LN mice. Tim-1 notably inhibited IgG-induced inflammatory responses in podocytes via reducing tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β expression, and it could protect podocytes against LN-induced injury via inducing autophagy. Meanwhile, Tim-1 significantly promoted the proliferation of IgG-induced podocytes via inhibiting apoptosis. The autophagy inhibitor reversed the effect of Tim-1 on inflammatory cytokines and autophagy-related proteins in IgG-treated podocytes.

Tim-1 protects podocytes against LN-induced injury via mediating autophagy, which might serve as a new target for the treatment of LN.