Hepatic connective tissue growth factor expression and regulation differ between non-steatotic and non-alcoholic steatotic livers from brain-dead donor

• Published in: Scientific reports Vol. 11; no. 1; p. 3857
• Main Authors: Yang, Dong-Jing, Shi, Ji-Hua, Xia, Zong-Ping, Guo, Wen-Zhi, Ahmed, Mohammed Shakil, Zhang, Shui-Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-02-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4017; 692/4020/4021/288; Animal models; Animals; Biomarkers - metabolism; Brain Death; Connective tissue; Connective tissue diseases; Connective tissue growth factor; Connective Tissue Growth Factor - metabolism; Death; Enzyme-linked immunosorbent assay; Fatty liver; Growth factors; Humanities and Social Sciences; Humans; Hypoxia; Immunohistochemistry; Liver; Liver - metabolism; Liver diseases; Male; Mortality; multidisciplinary; Non-alcoholic Fatty Liver Disease - metabolism; Polymerase chain reaction; Rats; Rats, Inbred Lew; Reverse transcription; Science; Science (multidisciplinary); siRNA; Steatosis; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; YAP-Signaling Proteins - metabolism; Yes-associated protein
• ISSN: 2045-2322; 2045-2322
• 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.