NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-β信号通路与Ⅱ型糖尿病临床相关性研究

被引:22
作者
胡龙江 [1 ]
周音频 [1 ]
曹运兰 [2 ]
吕湛 [3 ]
蓝运竞 [1 ]
宁琳 [1 ]
向立权 [1 ]
肖鹏 [1 ]
机构
[1] 重庆市涪陵中心医院心血管内科
[2] 贵州省人民医院心血管内科
[3] 川北医学院附属医院心血管内科
关键词
NLRP3炎性小体; Ⅱ型糖尿病; 白细胞介素-18; 白细胞介素-1β; 转化生长因子-β;
D O I
暂无
中图分类号
R587.1 [糖尿病];
学科分类号
100201 [内科学];
摘要
目的探讨NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-β信号通路与初诊Ⅱ型糖尿病(T2DM)的临床相关性。方法入选符合纳入标准的健康对照组30例及T2DM组40例,收集所有研究对象的一般临床资料,采用RTqPCR检测各组患者外周单个核细胞(PBMCs)中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体各组分mRNA的表达水平,Western blot法检测其蛋白表达水平,并采用ELISA法测定各组患者空腹血浆白介素-1β(IL-1β)、白介素-18(IL-18)、转化生长因子-β(TGF-β)水平。结果 PBMCs中NLRP3、凋亡相关微粒蛋白(ASC)、半胱氨酸蛋白酶-1(caspase-1)mRNA表达水平在T2DM组和对照组之间无显著性差异(P>0.05),但ASCmRNA在T2DM组与总胆固醇(TC)呈正相关(P<0.05);Caspase-1mRNA在T2DM组与体重指数(BMI)呈正相关(P<0.05)。PBMCs中NLRP3、ASC、Caspase-1表达水平及血浆IL-1β、IL-18、TGF-β水平在T2DM组和对照组之间有显著性差异(P<0.05),且ASC在T2DM组与平均动脉压(MAP)、空腹血糖(FPG)、TC、IL-1β、IL-18呈正相关(P<0.05);Caspase-1在T2DM组与吸烟、FPG、低密度脂蛋白胆固醇(LDL-C)、IL-1β呈正相关(P<0.05);IL-1β在T2DM组与TGF-β呈正相关(P<0.05)。结论以NLRP3炎性小体为中心的NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-β信号通路可能在初诊T2DM的发生发展过程中发挥重要作用。
引用
收藏
页码:335 / 340+346 +346
页数:7
相关论文
共 17 条
[1]
Dual role of interleukin-1β in islet amyloid formation and its β-cell toxicity: Implications for type 2 diabetes and islet transplantation [J].
Park, Yoo Jin ;
Warnock, Garth L. ;
Ao, Ziliang ;
Safikhan, Nooshin ;
Meloche, Mark ;
Asadi, Ali ;
Kieffer, Timothy J. ;
Marzban, Lucy .
DIABETES OBESITY & METABOLISM, 2017, 19 (05) :682-694
[2]
NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases.[J].Amna Abderrazak;Tatiana Syrovets;Dominique Couchie;Khadija El Hadri;Bertrand Friguet;Thomas Simmet;Mustapha Rouis.Redox Biology.2015,
[3]
Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies [J].
Zhao, Gang ;
Dharmadhikari, Gitanjali ;
Maedler, Kathrin ;
Meyer-Hermann, Michael .
PLOS COMPUTATIONAL BIOLOGY, 2014, 10 (08)
[4]
The complex regulation of TGF-? in cardiovascular disease.[J].Santiago Redondo;Marta Ramajo;Jorge Navarro-Dorado;Teresa Tejerina;Ursula Medina.Vascular Health and Risk Management.2012, defa
[5]
Transforming growth factor-β increases vascular smooth muscle cell proliferation through the Smad3 and extracellular signal-regulated kinase mitogen-activated protein kinases pathways [J].
Suwanabol, Pasithorn A. ;
Seedial, Stephen M. ;
Shi, Xudong ;
Zhang, Fan ;
Yamanouchi, Dai ;
Roenneburg, Drew ;
Liu, Bo ;
Kent, K. Craig .
JOURNAL OF VASCULAR SURGERY, 2012, 56 (02) :446-+
[6]
Transforming growth factor-β and atherosclerosis: interwoven atherogenic and atheroprotective aspects [J].
Toma, Ian ;
McCaffrey, Timothy A. .
CELL AND TISSUE RESEARCH, 2012, 347 (01) :155-175
[7]
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance [J].
Vandanmagsar, Bolormaa ;
Youm, Yun-Hee ;
Ravussin, Anthony ;
Galgani, Jose E. ;
Stadler, Krisztian ;
Mynatt, Randall L. ;
Ravussin, Eric ;
Stephens, Jacqueline M. ;
Dixit, Vishwa Deep .
NATURE MEDICINE, 2011, 17 (02) :179-U214
[8]
TNF-α Antagonism with Etanercept Decreases Glucose and Increases the Proportion of High Molecular Weight Adiponectin in Obese Subjects with Features of the Metabolic Syndrome [J].
Stanley, Takara L. ;
Zanni, Markella V. ;
Johnsen, Stine ;
Rasheed, Sarah ;
Makimura, Hideo ;
Lee, Hang ;
Khor, Victor K. ;
Ahima, Rexford S. ;
Grinspoon, Steven K. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2011, 96 (01) :E146-E150
[9]
Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes [J].
Masters, Seth L. ;
Dunne, Aisling ;
Subramanian, Shoba L. ;
Hull, Rebecca L. ;
Tannahill, Gillian M. ;
Sharp, Fiona A. ;
Becker, Christine ;
Franchi, Luigi ;
Yoshihara, Eiji ;
Chen, Zhe ;
Mullooly, Niamh ;
Mielke, Lisa A. ;
Harris, James ;
Coll, Rebecca C. ;
Mills, Kingston H. G. ;
Mok, K. Hun ;
Newsholme, Philip ;
Nunez, Gabriel ;
Yodoi, Junji ;
Kahn, Steven E. ;
Lavelle, Ed C. ;
O'Neill, Luke A. J. .
NATURE IMMUNOLOGY, 2010, 11 (10) :897-U1501
[10]
Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development..[J].Takimoto Tomohito;Wakabayashi Yu;Sekiya Takashi;Inoue Naoko;Morita Rimpei;Ichiyama Kenji;Takahashi Reiko;Asakawa Mayako;Muto Go;Mori Tomoaki;Hasegawa Eiichi;Saika Shizuya;Shizuya Saika;Hara Toshiro;Nomura Masatoshi;Yoshimura Akihiko.Journal of immunology (Baltimore; Md. : 1950).2010, 2