Cholangiopathy aggravation is caused by VDR ablation and alleviated by VDR-independent vitamin D signaling in ABCB4 knockout mice

Cholangiopathies are chronic liver diseases in which damaged cholangiocytes trigger a proinflammatory and profibrotic reaction. The nuclear vitamin D receptor (VDR) is highly expressed exerts immune-regulatory functions these cells. In the present study, we examined protective function of VDR other signaling pathways cholangiopathy cholangiocytes. Vdr was invalidated Abcb4 knockout mice, widely used animal model cholangiopathy. impact on features vivo (primary cell lines). Cholangiopathy (i.e, cholestasis, ductular reaction fibrosis) were aggravated Vdr;Abcb4 double mice compared to simple knockout, associated with an overexpression factors. phenotype also exacerbated following silencing vitro. expression factors severity reduced treated analog calcipotriol or D. vitro, inflammatory response TNFα significantly by biliary cells silenced for VDR, this effect abolished co-silencing plasma membrane D, protein disulfide-isomerase A3 (PDIA3). Our results demonstrate anti-inflammatory role They provide evidence PDIA3-mediated effects settings.