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

• Published in: Central-European journal of immunology Vol. 46; no. 3; pp. 305 - 313
• Main Authors: Yu, Yunxia, Zhu, Caixia, Yu, Nan, Yang, Lijuan
• Format: Journal Article
• Language: English
• Published: Poland Termedia Publishing House 01.01.2021
• Subjects: Apoptosis; Autophagy; Cholecystokinin; Cytokines; Experimental Immunology; Flow cytometry; Immunoglobulin G; Inflammation; Interleukin 1; Lupus; Lupus nephritis; lupus nephritis (ln); Nephritis; Phagocytosis; podocytes; Systemic lupus erythematosus; tim-1; Tumor necrosis factor; Tumor necrosis factor-TNF; lupus nephritis; autophagy; podocytes; Tim-1; lupus nephritis (LN)
• ISSN: 1426-3912; 1644-4124
• DOI: 10.5114/ceji.2021.109827

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.