Kupffer Cells Mediate Leptin-Induced Liver Fibrosis

摘要: BACKGROUND & AIMS: Leptin has profibrogenic effects in liver, although the mechanisms of this process are unclear. We sought to elucidate direct and indirect leptin on hepatic stellate cells (HSCs). METHODS: HSCs from Sprague-Dawley rats were exposed expression collagen-I, tissue inhibitor matrix metalloproteinases-1 (TIMP1), transforming growth factor beta 1 (TGF-beta 1), connective (CTGF/CCN2) was assessed. The medium Kupffer (KCs) sinusoidal endothelial (SECs) following evaluated HSCs; alpha-smooth muscle actin (alpha SMA) production KC signaling analyzed. RESULTS: not activated by incubation with leptin. However, cultured taken KCs that incubated had increased collagen 1, TIMP1, TGF-beta CTGF/CCN2, as well aSMA protein levels proliferation. These receptor dependent because conditioned isolated receptor-deficient Zucker (fa/fa) did activate HSCs. In leptin, messenger RNA CTGF/CCN2 increased. potentiated signal transducer activator transcription 3, AKT, extracellular signal-related kinase 1/2 phosphorylation AP-1 nuclear factor-kappa B DNA binding. Finally, addition anti-TGF-beta KC-conditioned inhibited HSC I, whereas 3 attenuated KC. CONCLUSIONS: mediates activation liver fibrosis through KC; these partly mediated 1.