NLRC5 inhibits neointima formation following vascular injury and directly interacts with PPARγ
NLRC5 inhibits neointima formation following vascular injury and directly interacts with PPARγ
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NLRC5 抑制血管损伤后新内膜形成并直接与 PPAR gamma 相互作用
DOI：
10.1038/s41467-019-10784-y
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发表时间：
2019-06-28
影响因子：
16.6
通讯作者：
Peng, Wenhui
中科院分区：
文献类型：
--
作者：
Luan, Peipei;Jian, Weixia;Peng, Wenhui
NLR家族CARD结构域5（NLRC 5）是天然免疫中重要的免疫调节因子，参与调节炎症和抗原呈递。然而，NLRC 5在血管重塑中的作用仍然未知。在这里，我们报告NLRC 5在血管重塑中的作用，并提供更好的理解其潜在的机制。与野生型小鼠相比，Nlrc 5敲除（Nlrc 5（-/-））小鼠在颈动脉结扎后表现出更严重的内膜增生。离体数据显示NLRC 5缺陷导致人主动脉平滑肌细胞（HASMC）的增殖和迁移增加。NLRC 5结合至PPAR γ并抑制HASMC去分化。NLRC 5的NACHT结构域对于与PPAR γ的相互作用和刺激PPAR γ活性是必需的。吡格列酮可显著挽救NLRC 5（-/-）小鼠的过度内膜增生，并减弱NLRC 5缺陷型HASMC的增殖和去分化。我们的研究表明，NLRC 5通过与PPAR γ相互作用直接抑制SMC功能障碍来调节血管重塑。
NLR Family CARD Domain Containing 5 (NLRC5), an important immune regulator in innate immunity, is involved in regulating inflammation and antigen presentation. However, the role of NLRC5 in vascular remodeling remains unknown. Here we report the role of NLRC5 on vascular remodeling and provide a better understanding of its underlying mechanism. Nlrc5 knockout (Nlrc5(-/-)) mice exhibit more severe intimal hyperplasia compared with wild-type mice after carotid ligation. Ex vivo data shows that NLRC5 deficiency leads to increased proliferation and migration of human aortic smooth muscle cells (HASMCs). NLRC5 binds to PPAR gamma and inhibits HASMC dedifferentiation. NACHT domain of NLRC5 is essential for the interaction with PPAR gamma and stimulation of PPAR gamma activity. Pioglitazone significantly rescues excessive intimal hyperplasia in Nlrc5(-/-) mice and attenuates the increased proliferation and dedifferentiation in NLRC5-deficient HASMCs. Our study demonstrates that NLRC5 regulates vascular remodeling by directly inhibiting SMC dysfunction via its interaction with PPAR gamma.