Spatial molecular and cellular determinants of STAT3 activation in liver fibrosis progression in non-alcoholic fatty liver disease

Autor: Jingjing Jiao, Jessica I. Sanchez, Omar A. Saldarriaga, Luisa M. Solis, David J. Tweardy, Dipen M. Maru, Heather L. Stevenson, Laura Beretta
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: JHEP Reports, Vol 5, Iss 2, Pp 100628- (2023)
Druh dokumentu: article
ISSN: 2589-5559
DOI: 10.1016/j.jhepr.2022.100628
Popis: Background & Aims: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice. Methods: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and transcriptomic changes in fibrotic NAFLD livers.Results: pSTAT3 scores in non-hepatocyte areas progressively increased with fibrosis severity (r = 0.53, p
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