Caspase-11 介导的肝细胞细胞焦亡促进非酒精性脂肪性肝炎的进展。
Caspase-11-Mediated Hepatocytic Pyroptosis Promotes the Progression of Nonalcoholic Steatohepatitis.
机构信息
Department of Gastroenterology, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, China; Department of Gastroenterology, Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China.
Department of Gastroenterology, Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China.
出版信息
Cell Mol Gastroenterol Hepatol. 2021;12(2):653-664. doi: 10.1016/j.jcmgh.2021.04.009. Epub 2021 Apr 21.
BACKGROUND
Nonalcoholic steatohepatitis (NASH) is an inflammatory disease with severe outcomes. Hepatocyte death, including apoptosis, necrosis, and pyroptosis, has been implicated in pathophysiology of NASH. Pyroptosis is mediated by inflammasome activation pathways including caspase-1-mediated canonical signaling pathway and caspase-11-mediated noncanonical signaling pathway. Until now, the precise role of caspase-11 in NASH remains unknown. In the present study, the potential roles of caspase-11 in NASH were explored.
METHODS
We established methionine- and choline-deficient diet (MCD)-induced NASH mice model using wild-type caspase-11-deficient mice. The expression of caspase-11, liver injury, fibrosis, inflammation, and activation of gasdermin D and interleukin-1β were evaluated.
RESULTS
Upregulated caspase-11 was detected in liver of mice with NASH. MCD-treated caspase-11-deficient mice had significantly decreased liver injury, fibrosis, and inflammation. The activation of gasdermin D and interleukin-1β was inhibited in caspase-11-deficient mice after MCD treatment. Overexpression of caspase-11 promoted steatohepatitis.
CONCLUSIONS
Caspase-11-mediated hepatocytic pyroptosis promotes the progression of NASH.
背景
非酒精性脂肪性肝炎（NASH）是一种具有严重后果的炎症性疾病。肝细胞死亡，包括凋亡、坏死和细胞焦亡，与 NASH 的病理生理学有关。细胞焦亡是由包含半胱氨酸蛋白酶-1（caspase-1）介导的经典信号通路和半胱氨酸蛋白酶-11（caspase-11）介导的非经典信号通路在内的多种炎症小体激活途径所介导的。到目前为止，caspase-11 在 NASH 中的确切作用仍不清楚。在本研究中，探索了 caspase-11 在 NASH 中的潜在作用。
方法
我们使用野生型 caspase-11 缺陷型小鼠建立了蛋氨酸和胆碱缺乏饮食（MCD）诱导的 NASH 小鼠模型。评估了 caspase-11、肝损伤、纤维化、炎症和 Gasdermin D 和白细胞介素-1β的激活情况。
结果
NASH 小鼠的肝脏中检测到上调的 caspase-11。MCD 处理的 caspase-11 缺陷型小鼠的肝损伤、纤维化和炎症明显减少。MCD 处理后，caspase-11 缺陷型小鼠中的 Gasdermin D 和白细胞介素-1β的激活受到抑制。caspase-11 的过表达促进了脂肪性肝炎。
结论
caspase-11 介导的肝细胞焦亡促进了 NASH 的进展。
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