Vitamin D Receptor Attenuates Hepatic Fibrosis in Mice — ASN Events

Vitamin D Receptor Attenuates Hepatic Fibrosis in Mice (#91)

Veronica F Lim 1 , Christopher Scott 1 , Jenny E Gunton 1
  1. Garvan Institute of Medical Research, Sydney, Australia

Vitamin D signalling plays an important role in inflammation and fibrosis in a number of tissues. Recent studies have demonstrated that the vitamin D receptor (VDR) is expressed in liver cells, especially hepatic stellate cells responsible for fibrogenesis. In chronic liver disease, vitamin D deficiency is associated with more severe fibrosis progression, but whether this is causal, or an effect of impaired hepatic 25-hydroxylation of vitamin D is unknown.

Methods. We tested the effect of VDR deletion on liver fibrosis in response to a known liver toxin (thioacetamide). VDR knockout, heterozygous and wild type mice received oral thioacetamide ad 0.3g/L in drinking water for 10-12 weeks.

Results. Livers of VDR knockout mice displayed the most fibrosis (average 2.65 on METAVIR score). Quantitation of collagen content was also increased by ~2.5-fold in VDR-null mice.

Real-time PCR (table A and B) showed that VDR knockout livers displayed greater expression of pro-fibrotic mRNAs, such as: Collagen-1-α, α-SMA (α-Smooth Muscle Actin), TIMP-1 (Tissue Inhibitor of Metalloproteinases-1) and MMP-9 (Matrix Metalloproteinase-9).

Conclusions. These studies strongly indicated that VDR inhibits liver pro-fibrotic gene expression and fibrosis. These findings are clinically relevant, as VDR is a potential therapeutic target for the resolution of hepatic fibrosis, and a high proportion of people with liver disease are vitamin D deficient.