A master cistromic circuit governing hepatic fibrogenesis [expression array]

Liver fibrosis is a reversible wound-healing response to liver injury and hepatic stellate cells (HSCs) are central cellular players that mediate hepatic fibrogenesis. However, the molecular mechanisms that govern this process remain unclear. Expression profiling was used to explore the potential impact of VDR signaling in TGFβ1 and TGFβ1+1,25(OH)2D3-treated primary rat HSCs. Notably, 1,25(OH)2D3 treatment attenuated the culture-induced activation of HSCs, such that the transcriptome of treated cells closely resembled that of freshly isolated quiescent cells (Figure 2A), and co-treatment of 1,25(OH)2D3 together with TGFβ resulted in considerable repression of a large set of TGFβ induced genes. We also demonstrated that in primary mouse HSCs, calcipotriol potently repressed fibrotic gene expression, suggesting that the anti-TGFβ properties of VDR agonists are likely conserved across mammalian species. Total RNA from primary rat HSCs were isolated and treated 1,25(OH)2D3 (100nM) for 24 hours to determine how Vitamin D ligands can impact the activated stellate cell state.