Department of Nephrology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430060, China.
Department of Endocrine, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan 430060, China.
Iran J Immunol. 2023 Sep 1;20(3):316-326. doi: 10.22034/iji.2023.97942.2541.
Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.
To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN.
MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism.
The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice.
ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice.
狼疮肾炎（LN）是指系统性红斑狼疮（SLE）累及肾脏引起的损伤。先前的研究发现血管生成素样蛋白 4（ANGPTL4）是一种新型尿生物标志物，可用于跟踪 LN 的疾病活动。
研究 ANGPTL4 在 LN 实验模型中的详细作用和调控机制。
11 周龄 MRL/lpr 小鼠注射腺相关病毒（AAV）介导的 ANGPTL4 短发夹 RNA（shRNA）。在 16 和 20 周龄时，收集 24 小时尿液样本以测量蛋白尿水平。处死小鼠后，采集血液和肾脏组织，检测血清肌酐（cr）和血尿素氮（BUN）水平、肾脏组织学变化和促炎细胞因子产生。此外，还检测了小鼠肾脏组织中 NLRP3 炎性小体相关分子的水平，以阐明其潜在机制。
AAV-sh-ANGPTL4 注射可显著降低 MRL/lpr 小鼠的蛋白尿、cr 和 BUN 水平。ANGPTL4 沉默可改善小鼠的肾小球、肾小管和间质损伤，减轻 LN 的病理改变。此外，ANGPTL4 敲低抑制了肾脏中促炎细胞因子的产生。机制上，ANGPTL4 抑制可抑制小鼠肾脏组织中 NLRP3 炎性小体的表达。
ANGPTL4 沉默抑制 NLRP3 炎性小体介导的炎症反应，从而改善 MRL/lpr 小鼠的 LN。
