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

Abstract

Introduction: 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. Aim of the study: To explore the expression and the potential regulatory molecular mechanism of Tim-1 in Ln-induced podocyte injury. Material and methods: 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. Results: 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. Conclusions: Tim-1 protects podocytes against Ln-induced injury via mediating autophagy, which might serve as a new target for the treatment of Ln. TED PRO