Molecular mechanisms underlying the protective effect of MIF in experimental liver fibrosis

TL;DRAbstract

Liver fibrosis, which is the replacement of functional liver tissue with scar tissue, is the characteristic result of all chronic liver diseases. Fibrogenesis is accompanied by inflammation and the activation of hepatic stellate cells (HSCs). These transdifferentiate into myofibroblasts and crucially contribute to the deposition of extracellular matrix and the remodeling of the existing matrix. Unexpectedly, macrophage migration inhibitory factor (MIF), a pleiotropic pro-inflammatory chemokine, attenuated hepatotoxin-induced liver fibrosis in mice. MIF-treated mice showed increases in HSC gene levels, suggesting increased myofibroblast activity following treatment. Leukocyte infiltrates, in contrast, were not affected by MIF treatment. While these data suggest that HSCs mediate MIF-induced protection, the molecular mechanisms underlying its effects have not yet been elucidated. In this work, hepatic cells, including immortalized and primary hepatocytes, Kupffer cells, and HSCs, were ch

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