Shrestha Nirajan, Chand Lokendra, Han Myung Kwan, Lee Seung Ok, Kim Chan Young, Jeong Yeon Jun
Laboratory of Liver Regeneration, Biomedical Research Institute, Chonbuk National University Hospital, 561-712, Jeonju, South Korea.
Department of Microbiology, Chonbuk National University Medical School, 561-712, Jeonju, South Korea.
Food Chem Toxicol. 2016 Jul;93:129-37. doi: 10.1016/j.fct.2016.04.024. Epub 2016 Apr 29.
Glutamine, traditionally a non-essential amino acid, now has been considered as essential in serious illness and injury. It is a major precursor for glutathione synthesis. However, the anti-fibrotic effect of glutamine and its molecular mechanism in experimental liver fibrosis have not been explored. In the present study we aimed to examine the potential role of glutamine in carbon tetrachloride (CCl4) induced liver fibrosis and TGF-β1 mediated epithelial mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Liver fibrosis was induced by intraperitoneal injection of CCl4 three times a week for 10 weeks. Glutamine treatment effectively attenuated liver injury and oxidative stress. Collagen content was significantly decreased in liver sections of glutamine treated mice compared to CCl4 model mice. Furthermore, glutamine decreased expression level of α-SMA and TGF-β in liver tissue. Our in vitro study showed that TGF-β1 treatment in hepatocytes resulted in loss of E-cadherin and increased expression of mesenchymal markers and EMT related transcription factor. In addition, TGF-β1 increased the expression of apoptotic markers. However, glutamine interestingly suppressed TGF-β1 mediated EMT and apoptosis. In conclusion, our results suggest that glutamine ameliorates CCl4 induced liver fibrosis and suppresses TGF-β1 induced EMT progression and apoptosis.
谷氨酰胺，传统上被认为是一种非必需氨基酸，现在已被视为在严重疾病和损伤中是必需的。它是谷胱甘肽合成的主要前体。然而，谷氨酰胺在实验性肝纤维化中的抗纤维化作用及其分子机制尚未得到探索。在本研究中，我们旨在研究谷氨酰胺在四氯化碳（CCl4）诱导的肝纤维化以及转化生长因子-β1（TGF-β1）介导的小鼠肝细胞上皮-间质转化（EMT）和凋亡中的潜在作用。通过每周腹腔注射3次CCl4，持续10周诱导肝纤维化。谷氨酰胺治疗有效地减轻了肝损伤和氧化应激。与CCl4模型小鼠相比，谷氨酰胺治疗的小鼠肝脏切片中的胶原蛋白含量显著降低。此外，谷氨酰胺降低了肝组织中α-平滑肌肌动蛋白（α-SMA）和TGF-β的表达水平。我们的体外研究表明，在肝细胞中用TGF-β1处理导致E-钙黏蛋白丢失，间充质标志物和EMT相关转录因子的表达增加。此外，TGF-β1增加了凋亡标志物的表达。然而，有趣的是，谷氨酰胺抑制了TGF-β1介导的EMT和凋亡。总之，我们的结果表明，谷氨酰胺可改善CCl4诱导的肝纤维化，并抑制TGF-β1诱导的EMT进展和凋亡。
