国内团队:小热休克蛋白CRYAB在结肠炎中的保护作用
创作:szx 审核:szx 2019年09月11日
  • 在IBD患者及DSS诱导的结肠炎小鼠模型中,αB-晶状体蛋白(CRYAB)的表达均显著降低,且与TNF-α及IL-6的水平呈负相关;
  • 在HT29及Caco-2细胞中过表达CRYAB,可通过抑制IKK复合物的形成而降低促炎因子(TNF-α、IL-6、IL-1β、IL-8等)的表达,而缺失CRYAB促进了促炎因子的应答;
  • 腹腔注射TAT-CRYAB融合蛋白至DSS诱导的结肠炎小鼠中,可显著缓解小鼠的结肠炎并保护肠道屏障完整性。
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szx
αB-晶状体蛋白(CRYAB)是一种小热休克蛋白,在肠道炎症中发挥保护性作用。由上海交通大学医学院附属新华医院结直肠外科杜鹏教授团队领衔,并在中科院苏州系统医学研究所杨义力教授、同济大学附属上海第十人民医院消化内科刘占举教授共同合作下在Mucosal Immunology上发表的一项最新研究,发现CRYAB可通过抑制IKKβ的活性,在体外降低细胞的炎症因子产生,并在结肠炎小鼠体内保护肠道屏障完整性并缓解结肠炎症状,提示CRYAB或是IBD的潜在治疗靶点。
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Mucosal Immunology [IF:6.726]

Small heat shock protein CRYAB inhibits intestinal mucosal inflammatory responses and protects barrier integrity through suppressing IKKβ activity

小热休克蛋白CRYAB通过抑制IKKβ活性以抑制肠道黏膜炎症应答并保护屏障完整性

10.1038/s41385-019-0198-5

2019-09-03, Article

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Alpha B-crystallin (CRYAB) is an important member of the small heat shock protein family, and plays a protective and therapeutic role in neurological inflammation. CRYAB expression was assessed in cultured HT29 and Caco-2 cells and inflamed mucosa of patients with inflammatory bowel disease (IBD) and colitis models in mice. Lentivirus-overexpressing and CRSIPR/Cas9 systems were used in different cells to upregulate and silence CRYAB expression, respectively. Cell permeable recombined fusion protein TAT-CRYAB was injected intraperitoneally into dextran sulfate sodium (DSS)- or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice to assess its anti-inflammatory effects. CRYAB was found to be significantly decreased in the inflamed mucosa from IBD patients and DSS-induced colitis in mice, and negatively correlated with the levels of TNF-α and IL-6, respectively. Enforced expression of CRYAB suppressed expression of proinflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, and IL-8) via inhibiting the IKK complex formation, whereas lack of CRYAB expression markedly enhanced proinflammatory responses. Consistently, administration of TAT-CRYAB fusion protein significantly alleviated DSS- or TNBS-induced colitis in mice and protected intestinal barrier integrity. CRYAB regulates inflammatory response in intestinal mucosa by inhibiting IKKβ-mediated signaling and may serve as a novel therapeutic approach in the treatment of IBD.

First Authors:
Weimin Xu

Correspondence Authors:
Zhanju Liu,Yili Yang,Peng Du

All Authors:
Weimin Xu,Yuegui Guo,Zhenyu Huang,Haoxin Zhao,Mingxia Zhou,Yuji Huang,Dongpeng Wen,Jinglue Song,Zhehui Zhu,Mingming Sun,Chen-Ying Liu,Yingwei Chen,Long Cui,Xiaolei Wang,Zhanju Liu,Yili Yang,Peng Du

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