Heat shock transcription factor 2 inhibits intestinal epithelial cell apoptosis through the mitochondrial pathway in ulcerative colitis
Heat shock transcription factor 2 inhibits intestinal epithelial cell apoptosis through the mitochondrial pathway in ulcerative colitis
复制标题
热休克转录因子 2 通过线粒体途径抑制溃疡性结肠炎肠上皮细胞凋亡。
DOI：
10.1016/j.bbrc.2020.04.103
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发表时间：
2020-06-18
影响因子：
3.1
通讯作者：
Miao, Yinglei
中科院分区：
文献类型：
--
作者：
Wang, Wen;Zhang, Fengrui;Miao, Yinglei
UC是一种慢性结肠黏膜炎症性疾病，发病机制不明，缺乏有效的治疗方法。肠上皮细胞过度凋亡破坏了肠上皮屏障，参与了UC的发生发展，但其机制尚不清楚。热休克蛋白在维持体内平衡和通过线粒体途径调节细胞凋亡方面起着重要作用。在我们以前的研究中，HSF2是HSPs的重要调节因子，在UC患者中高表达，并与小鼠和IECS的炎症呈负相关。因此，我们推测HSF2可能通过调节IECs的凋亡来预防肠粘膜炎。本研究首次采用DSS诱导的hsf2(-/-)小鼠结肠炎模型，探讨HSF2与IECs细胞凋亡的关系。WT+DSS组较WT+H2O组HSF2表达增强。KO+DSS组细胞凋亡程度较WT+DSS组严重。结果表明，HSF2与体内细胞凋亡呈负相关。慢病毒感染改变了Caco-2细胞中HSF2的表达，Bax、胞浆Cyto-C、裂解的Caspase-9和裂解的Caspase-3的表达与不同水平的HSF2呈负相关。这些结果表明，HSF2通过线粒体途径负向调节IECs的凋亡。这可能是HSF2在UC中发挥保护作用的可能机制之一。(C)2020 Elsevier Inc.保留所有权利。
UC is a chronic inflammatory disease of the colonic mucosa and lacks effective treatments because of unclear pathogenesis. Excessive apoptosis of IECs damages the intestinal epithelial barrier and is involved in the progression of UC, but the mechanism is unknown. HSPs are important in maintaining homeostasis and regulate apoptosis through the mitochondrial pathway. In our previous studies, HSF2, an important regulator of HSPs, was highly expressed in UC patients and negatively correlated with inflammation in mice and IECs. Therefore, we hypothesized that HSF2 may protect against intestinal mucositis by regulating the apoptosis of IECs. In this study, a DSS-induced colitis model of hsf2(-/-) mice was used to explore the relationship between HSF2 and apoptosis in IECs for the first time. The expression of HSF2 increased in the WT + DSS group compared with that in the WT + H2O group. Moreover, the extent of apoptosis was more severe in the KO + DSS group than in the WT + DSS group. The results showed that HSF2 was negatively correlated with apoptosis in vivo. The expression of HSF2 in Caco-2 cells was changed by lentiviral transfection, and the expression of Bax, cytoplasmic Cyto-C, Cleaved Caspase-9 and Cleaved Caspase-3 were negatively correlated with the different levels of HSF2. These results suggest that HSF2 negatively regulates apoptosis of IECs through the mitochondrial pathway. This may be one of the potential mechanisms to explain the protective role of HSF2 in UC. (c) 2020 Elsevier Inc. All rights reserved.