Hepatic fibrosis is known as the accumulation of connective tissue secondary to chronic damage to the liver. Epithelial–mesenchymal transition (EMT) corresponding increase in liver fibrogenesis was shown with immunohistochemistry and PCR-based studies. Suberoylanilide hydroxamic acid (SAHA), a synthetic compound approved as a histone deacetylase inhibitor (HDAC) by the FDA to treat cutaneous T-cell lymphoma is under investigation for the treatment of lung and renal fibrosis. Experimental modeling for hepatic fibrosis can be constructed with an LX2 cell line isolated from human hepatic stellate cells (HSCs). In this study, we aimed to investigate the modulation of SAHA in the pathogenesis of liver fibrosis by detecting the levels of proteins; (E-cadherin (E-cad), N-cadherin (N-cad), Vimentin (Vim), and genes; E-cad, N-cad, Vim, transforming growth factor-beta (TGF-β), alpha-smooth muscle actin (α-SMA), type 1 collagen (COL1A1), type 3 collagen (COL3A1)) that play a significant role in EMT with the LX2 cell line. We also evaluated the action of SAHA with cell proliferation, clonogenic, and migration assay. Cell proliferation was performed by flow cytometry. All the protein levels were determined by Western blot analysis, and gene expression levels were measured by Real-Time PCR. Our study observed that SAHA treatment decreased cell viability, colony formation and migration in LX2 cells. We found that SAHA increased E-cad expression level, while it decreased N-cad, Vim, COL1A1, COL3A1, α-SMA TGF-β genes expression levels. SAHA decreased the level of E-cad, N-cad, and Vim protein levels. We thought that SAHA possesses potent antifibrotic and anti-EMT properties in LX2.

肝纤维化被称为继发于肝脏慢性损伤的结缔组织积聚。免疫组织化学和基于 PCR 的研究显示上皮 - 间充质转化 (EMT) 相应增加肝纤维化。Suberoylanilide 异羟肟酸 (SAHA) 是一种合成化合物，被 FDA 批准为组蛋白去乙酰化酶抑制剂 (HDAC)，用于治疗皮肤 T 细胞淋巴瘤，目前正在研究用于治疗肺和肾纤维化。可以使用从人肝星状细胞 (HSC) 中分离的 LX2 细胞系构建肝纤维化的实验模型。在本研究中，我们旨在通过检测蛋白质水平来研究 SAHA 在肝纤维化发病机制中的调节作用；(E-钙粘蛋白 (E-cad)、N-钙粘蛋白 (N-cad)、波形蛋白 (Vim) 和基因；E-cad、N-cad、Vim、转化生长因子-β (TGF-β)、α-平滑肌肌动蛋白 (α-SMA)、1 型胶原蛋白 (COL1A1)、3 型胶原蛋白 (COL3A1)）在 LX2 细胞系的 EMT 中发挥重要作用。我们还通过细胞增殖、克隆形成和迁移试验评估了 SAHA 的作用。通过流式细胞术进行细胞增殖。所有蛋白质水平通过蛋白质印迹分析确定，基因表达水平通过实时PCR测量。我们的研究观察到 SAHA 处理降低了 LX2 细胞的细胞活力、集落形成和迁移。我们发现 SAHA 增加了 E-cad 的表达水平，而它降低了 N-cad、Vim、COL1A1、COL3A1、α-SMA TGF-β 基因的表达水平。SAHA 降低了 E-cad、N-cad 和 Vim 蛋白水平。我们认为 SAHA 在 LX2 中具有有效的抗纤维化和抗 EMT 特性。