Fatty Acids Activate the Transcriptional Coactivator YAP1 to Promote Liver Fibrosis via p38 Mitogen-Activated Protein Kinase

• Published in: Cellular and molecular gastroenterology and hepatology Vol. 12; no. 4; pp. 1297 - 1310
• Main Authors: Salloum, Shadi, Jeyarajan, Andre J, Kruger, Annie J, Holmes, Jacinta A, Shao, Tuo, Sojoodi, Mozhdeh, Kim, Myung-Ho, Zhuo, Zhu, Shroff, Stuti G, Kassa, Andrew, Corey, Kathleen E, Khan, Sanjoy K, Lin, Wenyu, Alatrakchi, Nadia, Schaefer, Esperance A.K, Chung, Raymond T
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021; Elsevier
• Subjects: Animals; Biomarkers; Computational Biology - methods; Disease Models, Animal; Disease Progression; Disease Susceptibility; Fatty Acids - metabolism; Female; Fibrosis; Gastroenterology and Hepatology; Gene Expression Profiling; Gene Expression Regulation; Hepatocytes - metabolism; Humans; Immunohistochemistry; Liver Cirrhosis - etiology; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver Function Tests; Male; Mice; Models, Biological; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - pathology; Nonalcoholic Fatty Liver Disease; Original Research; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; YAP; YAP-Signaling Proteins - metabolism; FFA; extracellular signal-regulated kinase; JNK; small interfering RNA; high fat diet; nonalcoholic steatohepatitis; α-SMA; shRNA; short hairpin RNA; pHSC; hepatocellular carcinoma; c-Jun N-terminal kinase; IL; HCC; MAPK; p38 MAPK; green fluorescent protein; choline-deficient; simple steatosis; Massachusetts General Hospital; Fibrosis; CDAHFD; primary human hepatocyte; ERK; α-smooth muscle actin; NAFLD; NT; YAP; mRNA; GFP; mitogen-activated protein kinase; PHH; messenger RNA; interleukin; WT; knockout; lipid droplet; RNA sequencing; SS; KO; siRNA; NASH; RNAseq; ECM; MGH; L-amino acid defined; nontargeting; free fatty acid; Nonalcoholic Fatty Liver Disease; LD; wild-type; extracellular matrix; primary human hepatic stellate cell

Background & AimsPatients with simple steatosis (SS) and nonalcoholic steatohepatitis can develop progressive liver fibrosis, which is associated with liver-related mortality. The mechanisms contributing to liver fibrosis development in SS, however, are poorly understood. SS is characterized by...