{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kang J"],"funding":["NIDDK NIH HHS","NCI NIH HHS","National Institutes of Health"],"pagination":["e165369"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9977430"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(3)"],"pubmed_abstract":["Patients with nonalcoholic steatohepatitis (NASH) have increased expression of liver monocyte chemoattractant protein-1 (MCP-1), but its cellular source and contribution to various aspects of NASH pathophysiology remain debated. We demonstrated increased liver CCL2 (which encodes MCP-1) expression in patients with NASH, and commensurately, a 100-fold increase in hepatocyte Ccl2 expression in a mouse model of NASH, accompanied by increased liver monocyte-derived macrophage (MoMF) infiltrate and liver fibrosis. To test repercussions of increased hepatocyte-derived MCP-1, we generated hepatocyte-specific Ccl2-knockout mice, which showed reduced liver MoMF infiltrate as well as decreased liver fibrosis. Forced hepatocyte MCP-1 expression provoked the opposite phenotype in chow-fed wild-type mi"],"journal":["JCI insight"],"pubmed_title":["Notch-mediated hepatocyte MCP-1 secretion causes liver fibrosis."],"pmcid":["PMC9977430"],"funding_grant_id":["R01 DK119767","P30 CA008748","P30 DK063608","R01 DK103818","DK103818,DK119767","R01 DK066525"],"pubmed_authors":["Dongiovanni P","Valenti L","Kim K","Dapito DH","Mayfield B","Yu J","Zhu C","Creusot RJ","Pajvani UB","Bartolome A","Postigo-Fernandez J","Meroni M","Kang J","Ferrante AW"],"additional_accession":[]},"is_claimable":false,"name":"Notch-mediated hepatocyte MCP-1 secretion causes liver fibrosis.","description":"Patients with nonalcoholic steatohepatitis (NASH) have increased expression of liver monocyte chemoattractant protein-1 (MCP-1), but its cellular source and contribution to various aspects of NASH pathophysiology remain debated. We demonstrated increased liver CCL2 (which encodes MCP-1) expression in patients with NASH, and commensurately, a 100-fold increase in hepatocyte Ccl2 expression in a mouse model of NASH, accompanied by increased liver monocyte-derived macrophage (MoMF) infiltrate and liver fibrosis. To test repercussions of increased hepatocyte-derived MCP-1, we generated hepatocyte-specific Ccl2-knockout mice, which showed reduced liver MoMF infiltrate as well as decreased liver fibrosis. Forced hepatocyte MCP-1 expression provoked the opposite phenotype in chow-fed wild-type mi","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-04T20:09:37.953Z","creation":"2025-04-04T20:09:37.953Z"},"accession":"S-EPMC9977430","cross_references":{"pubmed":["36752206"],"doi":["10.1172/jci.insight.165369"]}}