Butyrate-induced autophagy and anti-inflammatory effects of IECs plays an important role in UC. HSP has been proved to be associated with autophagy. HSF2, as an important regulator of HSP, has been determined to be highly expressed in UC. This study was designed to elucidate the relationship between HSF2, butyrate and epithelial autophagy and the potential mechanism of HSF2-related autophagy in UC. The autophagy levels and HSF2 expression in intestinal mucosa were increased in UC patients compared to controls. In DSS colitis models, hsf2-/- mice exhibited more severe intestinal inflammation and lower autophagy levels than wild-type mice. HSF2 expression could be induced by sodium butyrate and LPS as a dose-response relationship in HT-29 cells, epigenetically via increasing histone acetylation levels at the promoter region by sodium butyrate. Autophagy induced by sodium butyrate was promoted by overexpression HSF2 in HT-29 cells. Moreover, overexpression HSF2 decreased the expression and phosphorylation levels of PI3K, Akt and mTOR induced by sodium butyrate. HSF2 might induced by sodium butyrate and inflammation and played protective roles in UC by enhancing autophagy of IECs. This indicated that HSF2 may be a critical target for autophagy modulation and a new potential therapeutic target in UC.

中文翻译：

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热休克转录因子2通过抑制溃疡性结肠炎中的mTOR促进丁酸钠诱导的自噬。

丁酸酯引起的IEC自噬和抗炎作用在UC中起重要作用。HSP已被证明与自噬有关。HSF2作为HSP的重要调节剂，已确定在UC中高表达。本研究旨在阐明UC中HSF2，丁酸与上皮自噬之间的关系以及HSF2相关自噬的潜在机制。与对照组相比，UC患者肠粘膜中的自噬水平和HSF2表达增加。在DSS结肠炎模型中，hsf2-/-小鼠比野生型小鼠表现出更严重的肠道炎症和更低的自噬水平。HSF2表达可以由丁酸钠和LPS诱导为HT-29细胞中的剂量反应关系，表观遗传上通过丁酸钠增加启动子区域的组蛋白乙酰化水平来实现。HSF2在HT-29细胞中的过度表达促进了丁酸钠的自噬。此外，过表达HSF2降低了丁酸钠诱导的PI3K，Akt和mTOR的表达和磷酸化水平。HSF2可能由丁酸钠和炎症诱导，并通过增强IECs的自噬而在UC中起保护作用。这表明HSF2可能是自噬调节的关键靶标，也是UC中新的潜在治疗靶标。