Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation and Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Sci Rep. 2021 Feb 16;11(1):3857. doi: 10.1038/s41598-021-83516-2.
Accurate evaluation of liver steatosis is required from brain-dead donors (BDDs) with nonalcoholic fatty liver disease (NAFLD). Our purposes were to investigate expression and regulation of connective tissue growth factor (CTGF) expression in livers from human and rat after brain death, and further evaluate its potential application. NAFLD and brain death models were established in rats. LX2 cells were cultured under hypoxia/reoxygenation. CTGF protein and mRNA levels were measured in liver samples from BDDs of human and rat by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. YAP-regulated CTGF expression was investigated in LX2 cells via YAP small interfering RNA and Verteporfin treatment. Blood CTGF level from BDDs was measured by enzyme-linked immunosorbent assay. After brain death, CTGF, transforming growth factor-β and YAP were overexpressed in non-alcoholic steatotic liver, whereas CTGF was downregulated in non-steatotic liver. Time-series analysis revealed that CTGF and YAP expression was comparable, as confirmed by inhibited YAP expression in LX2 cells. CTGF level and NAFLD activity were linearly correlated. CTGF expression and regulation differ between non-steatosis and nonalcoholic steatosis livers from BDDs. CTGF may be an important factor to evaluate graft quality from BDDs with NAFLD.
准确评估脑死亡供体(BDD)的非酒精性脂肪肝(NAFLD)需要。我们的目的是研究脑死亡后人类和大鼠肝脏中结缔组织生长因子(CTGF)表达的变化及其调控机制,并进一步评估其潜在的应用价值。在大鼠中建立了 NAFLD 和脑死亡模型。在缺氧/复氧条件下培养 LX2 细胞。通过免疫组织化学和逆转录定量聚合酶链反应检测人类和大鼠 BDD 肝脏样本中 CTGF 蛋白和 mRNA 水平。通过 YAP 小干扰 RNA 和 Verteporfin 处理研究 LX2 细胞中 YAP 调节的 CTGF 表达。通过酶联免疫吸附试验测量 BDD 的血 CTGF 水平。脑死亡后,非酒精性脂肪性肝中 CTGF、转化生长因子-β和 YAP 过度表达,而非脂肪性肝中 CTGF 下调。时间序列分析显示 CTGF 和 YAP 表达具有可比性,LX2 细胞中 YAP 表达抑制得到证实。CTGF 水平与 NAFLD 活动呈线性相关。BDD 的非脂肪变性和非酒精性脂肪性肝中 CTGF 的表达和调控不同。CTGF 可能是评估 NAFLD BDD 移植物质量的重要因素。