Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine (Jinyun Branch), Jinyun, Zhejiang 321400, P.R. China.
Int J Mol Med. 2019 Jan;43(1):103-116. doi: 10.3892/ijmm.2018.3950. Epub 2018 Oct 23.
Liver fibrosis is a serious threat to human health, and there is currently no effective clinical drug for treatment of the disease. Although Galectin‑1 is effective, its role in liver function, inflammation, matrix metalloproteinases and the activation of hepatic stellate cells (HSCs) remains to be elucidated. The aim of the present study was to elucidate the effect of Galectin‑1 on the activation, proliferation and apoptosis of HSCs in a mouse model of liver fibrosis. Following successful model establishment and tissue collection, mouse HSCs (mHSCs) were identified and an mHSC line was constructed. Subsequently, to determine the role of Galectin‑1 in liver fibrosis, the expression levels of transforming growth factor (TGF)‑β1, connective tissue growth factor (CTGF) and α‑smooth muscle actin (α‑SMA) pre‑ and post‑transfection were evaluated by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. In addition, the effects of Galectin‑1 on the biological behavior and mitochondrial function of mHSCs were determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay, flow cytometry and a scratch test. It was first observed that the expression levels of Galectin‑1, TGF‑β1, CTGF and α‑SMA were downregulated by silencing the gene expression of Galectin‑1. Additionally, silencing the gene expression of Galectin‑1 inhibited cell cycle progression, proliferation and migration but induced the apoptosis of mHSCs from mice with liver fibrosis. Furthermore, the in vivo experimental results suggested that silencing the gene expression of Galectin‑1 improved liver fibrosis. Collectively, it was concluded that silencing the gene expression of Galectin‑1 ameliorates liver fibrosis and that functionally suppressing Galectin‑1 may be a future therapeutic strategy for liver fibrosis.
肝纤维化是严重威胁人类健康的疾病，目前尚无有效的临床治疗药物。尽管半乳糖凝集素-1（Galectin-1）具有一定疗效，但它在肝功能、炎症、基质金属蛋白酶和肝星状细胞（HSCs）激活中的作用仍有待阐明。本研究旨在探讨 Galectin-1 对肝纤维化小鼠模型中 HSCs 激活、增殖和凋亡的影响。成功建立模型并采集组织后，鉴定小鼠 HSCs（mHSCs）并构建 mHSC 系。随后，为了研究 Galectin-1 在肝纤维化中的作用，通过逆转录-定量聚合酶链反应和 Western blot 分析评估转染前后转化生长因子（TGF）-β1、结缔组织生长因子（CTGF）和α-平滑肌肌动蛋白（α-SMA）的表达水平。此外，通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）比色法、流式细胞术和划痕试验检测 Galectin-1 对 mHSCs 生物学行为和线粒体功能的影响。结果表明，沉默 Galectin-1 基因表达后，Galectin-1、TGF-β1、CTGF 和 α-SMA 的表达水平下调。此外，沉默 Galectin-1 基因表达可抑制肝纤维化小鼠 mHSCs 的细胞周期进程、增殖和迁移，并诱导其凋亡。体内实验结果表明，沉默 Galectin-1 基因表达可改善肝纤维化。综上所述，沉默 Galectin-1 基因表达可改善肝纤维化，功能抑制 Galectin-1 可能成为肝纤维化的未来治疗策略。
