Krüppel 样因子 10 (KLF10) 参与调节转化生长因子 β (TGFβ) 信号传导的正反馈回路，TGFβ 在肝病的发病机制中发挥着重要作用。在这里，我们研究了 KLF10 缺失是否会影响肝纤维化和肝细胞癌 (HCC) 的发展。我们在 C57BL/6 小鼠中诱导 KLF10 缺失。肝纤维化是通过高脂肪和高蔗糖饮食（高脂饮食[HFD]）诱导的，而肝癌是通过腹膜内给予N-二乙基亚硝胺（DEN）产生的。使用 Hep3B 和 LX2 细胞进行体外实验来评估 KLF10 在癌症微环境中的作用。使用来自 60 名接受肝切除的患者的人类 HCC 样本对 KLF10 表达进行了免疫组织化学研究。KLF10 缺失导致 DEN 诱导的 HCC 负担增加，同时 SMAD2 显着上调，尽管 KLF10 的缺失并没有改变 HFD 诱导的肝纤维化。经过 DEN 处理的 KLF10 缺失小鼠表现出间充质标记物（N-钙粘蛋白和 SNAI2）和肿瘤转移标记物（基质金属蛋白酶 2 和 9）水平升高。使用 siRNA 去除 Hep3B 和 LX2 细胞中的 KLF10 与侵袭性增加相关。与KLF10保存的Hep3B细胞和KLF10完整的LX2细胞的共培养相比，KLF10保存的Hep3B细胞和KLF10耗尽的LX2细胞的共培养导致侵袭显着增强。切除的人类 HCC 标本中 KLF10 表达低与生存率低相关。这项研究的结果表明，KLF10 的缺失会通过 TGFβ 信号传导的改变促进肝癌的发展。© 2023。作者。

Krüppel-like factor 10 (KLF10) is involved in a positive feedback loop that regulates transforming growth factor β (TGFβ) signaling, and TGFβ plays an important role in the pathogenesis of liver disease. Here, we investigated whether KLF10 deletion affects the development of liver fibrosis and hepatocellular carcinoma (HCC).We induced KLF10 deletion in C57BL/6 mice. Liver fibrosis was induced by feeding a diet high in fat and sucrose (high-fat diet [HFD]), whereas HCC was produced by intraperitoneal administration of N-diethylnitrosamine (DEN). An in vitro experiment was performed to evaluate the role of KLF10 in the cancer microenvironment using Hep3B and LX2 cells. An immunohistochemical study of KLF10 expression was performed using human HCC samples from 60 patients who had undergone liver resection.KLF10 deletion resulted in an increased DEN-induced HCC burden with significant upregulation of SMAD2, although loss of KLF10 did not alter HFD-induced liver fibrosis. DEN-treated mice with KLF10 deletion exhibited increased levels of mesenchymal markers (N-cadherin and SNAI2) and tumor metastasis markers (matrix metalloproteinases 2 and 9). KLF10 depletion in Hep3B and LX2 cells using siRNA was associated with increased invasiveness. Compared with co-culture of KLF10-preserved Hep3B cells and KLF10-intact LX2 cells, co-culture of KLF10-preserved Hep3B cells and KLF10-depleted LX2 cells resulted in significantly enhanced invasion. Low KLF10 expression in resected human HCC specimens was associated with poor survival.The results of this study suggest that loss of KLF10 facilitates liver cancer development with alteration in TGFβ signaling.© 2023. The Author(s).