CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis.
CTRP3 ameliorates cerulein-induced severe acute pancreatitis in mice via SIRT1/NF-κB/p53 axis.
复制标题
CTRP3通过SIRT1/NF-κB/p53轴来缓解小鼠塞洛蛋白诱导的严重急性胰腺炎。
DOI：
10.1042/bsr20200092
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发表时间：
2020-10-30
影响因子：
4
通讯作者：
Ding Z
中科院分区：
文献类型：
--
作者：
Lv C;He Y;Wei M;Xu G;Chen C;Xu Z;Ding Z
重症急性胰腺炎(SAP)是临床上常见且危及生命的急腹症。C1q/肿瘤坏死因子相关蛋白3(CTRP3)是一种新的脂联素类似物，已被认为是多种炎症性疾病的重要调节因子。然而，CTRP3在SAP中的生物学作用仍然知之甚少。本研究旨在研究CTRP3在SAP中的作用，并阐明其可能的机制。在本研究中，每小时腹腔注射雨蛙素(50μg/kg)，并在末次注射雨蛙素后立即腹腔注射脂多糖(10 mg/kg)，建立重症急性胰腺炎动物模型。组织学检查和血清学分析表明，SAP小鼠模型建立成功。在此，我们发现与正常对照组小鼠相比，SAP小鼠胰腺组织中CTRP3的表达显著降低。此外，我们还探讨了CTRP3在SAP小鼠中的拯救作用，发现CTRP3过表达可减轻病理损害，抑制炎症介质的释放，并抑制腺泡细胞的凋亡。值得注意的是，机制研究表明，CTRP3过表达抑制了NF-κB p65的磷酸化和P53的乙酰化，从而通过激活沉默信息调节因子1(SIRT1)，一种依赖于烟酰胺腺嘌呤二核苷酸的蛋白质去乙酰化，减轻了雨兰蛋白诱导的小鼠重症急性胰腺炎。综上所述，我们的数据表明，CTRP3可能通过调节SIRT1介导的NF-κB和P53信号通路在重症急性胰腺炎小鼠中发挥保护作用，这意味着一种有前景的治疗策略。
Severe acute pancreatitis (SAP) is a common and life-threatening clinical acute abdominal disease. C1q/tumor necrosis factor-related protein 3 (CTRP3), a novel paralog of adiponectin, has been identified as a crucial regulator in multiple types of inflammatory disorders. However, the biological role of CTRP3 in SAP remains poorly understood. The present study aimed to characterize the role of CTRP3 in SAP and illuminate the potential mechanisms involved. In the current study, SAP mouse models were induced by seven hourly intraperitoneal injection of cerulein (50 μg/kg) and an immediate intraperitoneal injection of lipopolysaccharide (10 mg/kg) after the last cerulein administration. Histological examination and serological analysis demonstrated that SAP mouse models were successfully established. Herein, we found that CTRP3 expression was significantly decreased in the pancreatic tissues of SAP mice compared with normal control mice. Furthermore, we explored the effects of CTRP3 rescue in SAP mice and discovered that CTRP3 overexpression attenuated pathological lesions, inhibited inflammatory mediator release and repressed acinar cell apoptosis. Notably, mechanistic studies revealed that CTRP3 overexpression suppressed NF-κB p65 phosphorylation and p53 acetylation to alleviate cerulein-induced SAP in mouse models through activation of silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent protein deacetylase. Collectively, our data indicate that CTRP3 may exert its protective effects in SAP mice via regulation of SIRT1-mediated NF-κB and p53 signaling pathways, implying a promising therapeutic strategy against SAP.