Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis
Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis
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DOI：
10.1038/s41467-019-10116-0
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发表时间：
2019-05-13
影响因子：
16.6
通讯作者：
Zou, Ming-Hui
中科院分区：
文献类型：
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作者：
Lu, Qiulun;Ma, Zejun;Zou, Ming-Hui
虽然血管紧张素II （AngII）已知可引起肾损伤和纤维化，但其潜在机制仍不清楚。在这里，我们发现高血压肾病（HN）患者和血管灌注小鼠表现出循环miR103a-3p水平升高。我们观察到miR-103a-3p水平与血管i诱导的肾功能障碍呈正相关。miR-103a-3p抑制肾小球内皮细胞中蔗糖非发酵相关丝氨酸/苏氨酸蛋白激酶SNRK的表达，HN患者肾小球和血管灌注小鼠肾小球显示SNRK内皮表达降低。我们发现SNRK通过与活化核因子κ B (nf - κ B)/p65相互作用发挥抗炎作用。总体而言，我们证明AngII增加循环miR-103a-3p水平，从而降低肾小球内皮细胞中的SNRK水平，导致NF-kappa B/p65过度激活，从而导致肾脏炎症和纤维化。总之，我们的工作确定了miR-103a-3p/SNRK/NF-kappa B/p65是血管i诱导的肾脏炎症和纤维化的调控轴。
Although angiotensin II (AngII) is known to cause renal injury and fibrosis, the underlying mechanisms remain poorly characterized. Here we show that hypertensive nephropathy (HN) patients and AngII-infused mice exhibit elevated levels of circulating miR103a-3p. We observe a positive correlation between miR-103a-3p levels and AngII-induced renal dysfunction. miR-103a-3p suppresses expression of the sucrose non-fermentable-related serine/threonine-protein kinase SNRK in glomerular endothelial cells, and glomeruli of HN patients and AngII-infused mice show reduced endothelial expression of SNRK. We find that SNRK exerts anti-inflammatory effects by interacting with activated nuclear factor-kappa B (NF-kappa B)/p65. Overall, we demonstrate that AngII increases circulating miR-103a-3p levels, which reduces SNRK levels in glomerular endothelial cells, resulting in the over-activation of NF-kappa B/p65 and, consequently, renal inflammation and fibrosis. Together, our work identifies miR-103a-3p/SNRK/NF-kappa B/p65 as a regulatory axis of AngII-induced renal inflammation and fibrosis.