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Heat shock transcription factor 2 inhibits intestinal epithelial cell apoptosis through the mitochondrial pathway in ulcerative colitis

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机构: [1]Kunming Med Univ, Yunnan Inst Digest Dis, Dept Gastroenterol, Affiliated Hosp 1, Kunming 650032, Yunnan, Peoples R China [2]First Hosp Changsha, Dept Respirat, Changsha 410005, Hunan, Peoples R China [3]Kunming Med Univ, Yunnan Inst Digest Dis, Affiliated Hosp 1, Dept Gen Surg, Kunming 650032, Yunnan, Peoples R China
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关键词: Heat shock transcription factor 2 Intestinal epithelial cell Apoptosis Mitochondrial pathway Ulcerative colitis Pathogenesis

摘要:
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.

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出版当年[2021]版:
大类 | 3 区 生物
小类 | 3 区 生物物理 4 区 生化与分子生物学
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生物物理 4 区 生化与分子生物学
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出版当年[2020]版:
Q2 BIOPHYSICS Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS

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第一作者机构: [1]Kunming Med Univ, Yunnan Inst Digest Dis, Dept Gastroenterol, Affiliated Hosp 1, Kunming 650032, Yunnan, Peoples R China
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通讯机构: [1]Kunming Med Univ, Yunnan Inst Digest Dis, Dept Gastroenterol, Affiliated Hosp 1, Kunming 650032, Yunnan, Peoples R China
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