European journal of pharmacology · 2026
14-3-3η protein ameliorates glomerular endothelial cell injury in lupus nephritis by regulating mTOR pathway-mediated autophagy.
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Song Xinghui, Tang Kaijiang, Gao Jinglin, Liu Xiuhua, Jiang Qijun, Ma Li
Аннотация
BACKGROUND: Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is characterized by glomerular endothelial cell injury, inflammation, and immune complex deposition. The 14-3-3η protein, a multifunctional regulator, plays roles in various cellular processes, however, its specific role in LN and the underlying mechanisms remain unclear. This study investigates the role of 14-3-3η in LN by modulating mTOR pathway-mediated autophagy.
METHODS: Human renal glomerular endothelial cells (HRGECs) overexpressing 14-3-3η were treated with plasma from healthy donors and LN patients. Cell viability, nitric oxide (NO) levels, and the expression of syndecan-1, VCAM-1, 14-3-3η, and autophagy markers (LC3, PINK1, Parkin) were analyzed. In vivo, an LN mouse model was established, and treated with 14-3-3η-overexpressing adenovirus or rapamycin (RAP) was administered. Renal histopathology, serum syndecan-1, VCAM-1, and autophagy markers were evaluated.
RESULTS: In vitro, 14-3-3η overexpression attenuated LN plasma-induced endothelial injury, enhanced cell viability, reduced NO levels, and downregulated syndecan-1 and VCAM-1 expression. It also suppressed autophagy by promoting mTORC1 complex formation and downstream signaling via mTOR S1276 phosphorylation. In vivo, 14-3-3η overexpression ameliorated glomerular pathology and inhibited autophagy by regulating mTOR, LC3, PINK1, and Parkin.
CONCLUSION: 14-3-3η alleviates LN-induced glomerular endothelial injury and renal dysfunction by modulating mTOR-mediated autophagy. This study identifies 14-3-3η as a potential therapeutic target for LN and advances the understanding of its role in kidney diseases.
METHODS: Human renal glomerular endothelial cells (HRGECs) overexpressing 14-3-3η were treated with plasma from healthy donors and LN patients. Cell viability, nitric oxide (NO) levels, and the expression of syndecan-1, VCAM-1, 14-3-3η, and autophagy markers (LC3, PINK1, Parkin) were analyzed. In vivo, an LN mouse model was established, and treated with 14-3-3η-overexpressing adenovirus or rapamycin (RAP) was administered. Renal histopathology, serum syndecan-1, VCAM-1, and autophagy markers were evaluated.
RESULTS: In vitro, 14-3-3η overexpression attenuated LN plasma-induced endothelial injury, enhanced cell viability, reduced NO levels, and downregulated syndecan-1 and VCAM-1 expression. It also suppressed autophagy by promoting mTORC1 complex formation and downstream signaling via mTOR S1276 phosphorylation. In vivo, 14-3-3η overexpression ameliorated glomerular pathology and inhibited autophagy by regulating mTOR, LC3, PINK1, and Parkin.
CONCLUSION: 14-3-3η alleviates LN-induced glomerular endothelial injury and renal dysfunction by modulating mTOR-mediated autophagy. This study identifies 14-3-3η as a potential therapeutic target for LN and advances the understanding of its role in kidney diseases.