Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB Signaling.
Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB Signaling.
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脂肪因子C1Q/肿瘤坏死因子 - 相关蛋白3（CTRP3）通过SIRTUIN 1/NF-κB信号传导减轻肠道炎症。
DOI：
10.1016/j.jcmgh.2022.12.013
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发表时间：
2023
影响因子：
7.2
通讯作者：
Wong, G. William
中科院分区：
文献类型：
--
作者：
Yu, Huimin;Zhang, Zixin;Li, Gangping;Feng, Yan;Xian, Lingling;Bakhsh, Fatemeh;Xu, Dongqing;Xu, Cheng;Vong, Tyrus;Wu, Bin;Selaru, Florin M.;Wan, Fengyi;Donowitz, Mark;Wong, G. William
脂肪因子CTRP 3在几种非肠道疾病中具有抗炎作用。尽管炎性肠病（IBD）患者的血清CTRP 3降低，但其在IBD中的功能尚未确定。在这里，我们阐明CTRP 3在肠道炎症中的功能。将CTRP 3敲除（KO）和过表达转基因（Tg）小鼠及其相应的野生型同窝仔沿着用葡聚糖硫酸钠处理6-10天。分析结肠炎表型和组织学数据。在源自CTRP 3 KO和Tg小鼠的鼠和人肠粘膜和小鼠肠类器官中检查CTRP 3介导的信号传导。CTRP 3 KO小鼠发生了更严重的结肠炎，而CTRP 3 Tg小鼠发生的结肠炎比野生型同窝小鼠不那么严重。CTRP 3的缺失与组蛋白脱乙酰酶SIRT-1水平降低、磷酸化/乙酰化NF-κB亚基p65水平升高以及促炎细胞因子肿瘤坏死因子-α和白细胞介素-6水平升高相关。CTRP 3 Tg小鼠的结果与CTRP 3 KO小鼠的结果相反。将SIRT 1激活剂白藜芦醇添加到KO肠类器官中，将SIRT 1抑制剂Ex-527添加到Tg肠类器官中，表明SIRT 1是CTRP 3相关炎症变化的下游效应子。在IBD患者中，观察到类似的CTRP 3/SIRT 1/NF-κB关系。CTRP 3表达水平与急性小鼠结肠炎模型和IBD患者的肠道炎症呈负相关。CTRP 3可能通过SIRT 1/NF-κB信号通路减轻肠道炎症反应。CTRP 3信号传导的操纵，包括通过使用SIRT 1激活剂，可以在IBD的治疗中提供翻译潜力。
The adipokine CTRP3 has anti-inflammatory effects in several nonintestinal disorders. Although serum CTRP3 is reduced in patients with inflammatory bowel disease (IBD), its function in IBD has not been established. Here, we elucidate the function of CTRP3 in intestinal inflammation. CTRP3 knockout (KO) and overexpressing transgenic (Tg) mice, along with their corresponding wild-type littermates, were treated with dextran sulfate sodium for 6–10 days. Colitis phenotypes and histologic data were analyzed. CTRP3-mediated signaling was examined in murine and human intestinal mucosa and mouse intestinal organoids derived from CTRP3 KO and Tg mice. CTRP3 KO mice developed more severe colitis, whereas CTRP3 Tg mice developed less severe colitis than wild-type littermates. The deletion of CTRP3 correlated with decreased levels of Sirtuin-1 (SIRT1), a histone deacetylase, and increased levels of phosphorylated/acetylated NF-κB subunit p65 and proinflammatory cytokines tumor necrosis factor-α and interleukin-6. Results from CTRP3 Tg mice were inverse to those from CTRP3 KO mice. The addition of SIRT1 activator resveratrol to KO intestinal organoids and SIRT1 inhibitor Ex-527 to Tg intestinal organoids suggest that SIRT1 is a downstream effector of CTRP3-related inflammatory changes. In patients with IBD, a similar CTRP3/SIRT1/NF-κB relationship was observed. CTRP3 expression levels correlate negatively with intestinal inflammation in acute mouse colitis models and patients with IBD. CTRP3 may attenuate intestinal inflammation via SIRT1/NF-κB signaling. The manipulation of CTRP3 signaling, including through the use of SIRT1 activators, may offer translational potential in the treatment of IBD.
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影响因子：
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影响因子：
3.7
作者：
Lo Sasso G;Ryu D;Mouchiroud L;Fernando SC;Anderson CL;Katsyuba E;Piersigilli A;Hottiger MO;Schoonjans K;Auwerx J
通讯作者：
Auwerx J