CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading

Autor: Xin Chu, Qunyan Jin, Hui Chen, G. Craig Wood, Anthony Petrick, William Strodel, Jon Gabrielsen, Peter Benotti, Tooraj Mirshahi, David J. Carey, Christopher D. Still, Johanna K. DiStefano, Glenn S. Gerhard
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-9 (2018)
Druh dokumentu: article
ISSN: 1479-5876
DOI: 10.1186/s12967-018-1490-y
Popis: Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood. Methods Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid loading were conducted in vitro using quantitative PCR and ELISA. Results Three orthogonal methods to profile human liver biopsy RNA each identified the chemokine CCL20 (CC chemokine ligand 20 or MIP-3 alpha) gene as one of the most up-regulated transcripts in NAFLD fibrosis relative to normal histology, validated in a replication group. CCL20 protein levels in serum measured in 224 NAFLD patients were increased in severe fibrosis (p
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