Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Cell Immunol. 2018 Jun;328:1-8. doi: 10.1016/j.cellimm.2018.02.013. Epub 2018 Feb 21.
Lupus nephritis is an immune-complexes mediated glomerulonephritis. Vascular lesions and endothelial cell injuries are common in lupus nephritis and important for renal damage. However, the precise mechanisms by which immune complexes lead to endothelial cell injuries are still unclear. Autophagy is a conserved metabolic process and shows protective roles in many cell types and diseases. In present study, we investigated whether immune complexes could affect autophagy and participate in endothelial dysfunctions. Heat-aggregated gamma globulin (HAGG) was used to substitute immune complexes. Glomerular endothelial cells (GECs) were incubated with HAGG and autophagy-related markers were evaluated. Results showed that HAGG suppressed autophagy in GECs, through Akt/mTOR-dependent pathway. The combination of HAGG and tumor necrosis factor-alpha suppressed autophagy in GECs and further decreased cell viabilities. The suppressed effects of HAGG on GECs autophagy and viability, especially under inflammatory microenvironment, may provide new views for explaining the mechanisms of renal impairments in lupus nephritis.
狼疮性肾炎是一种免疫复合物介导的肾小球肾炎。血管病变和内皮细胞损伤在狼疮性肾炎中很常见，对肾脏损害很重要。然而，免疫复合物如何导致内皮细胞损伤的确切机制尚不清楚。自噬是一种保守的代谢过程，在许多细胞类型和疾病中表现出保护作用。在本研究中，我们研究了免疫复合物是否会影响自噬并参与内皮功能障碍。热聚合γ球蛋白（HAGG）被用来替代免疫复合物。用 HAGG 孵育肾小球内皮细胞（GEC），并评估自噬相关标志物。结果表明，HAGG 通过 Akt/mTOR 依赖性途径抑制 GEC 中的自噬。HAGG 与肿瘤坏死因子-α的结合抑制了 GEC 中的自噬，并进一步降低了细胞活力。HAGG 对 GEC 自噬和活力的抑制作用，特别是在炎症微环境下，可能为解释狼疮性肾炎中肾脏损害的机制提供新的视角。
