Expression pattern of CYP24 in liver during ageing in long-term diabetes

Abstract

Association of liver calcitriol (active vitamin D metabolite) catabolism with osteomalacia during prolonged use of certain drugs was reported in several recent studies. To examine whether the increased calcitriol catabolism could be a potential link between ageing/diabetes mellitus (DM) and bone loss, we studied the dynamic of expression of CYP24, the main calcitriol catabolising enzyme in the liver of rats during ageing and a long-term experimental DM1. DM1 model was induced with intraperitoneally injected streptozotocin (STZ) (55mg/kg). Sprague-Dawley rats were sacrificed 6 and 12 months after the DM1 induction. The immunohistochemical analyses of CYP24 and transforming growth factor β 1 (TGF-β1) expression in the liver were performed. We found that ageing and long-term DM1 resulted in a significantly increased expression of CYP24 in hepatocytes, as well as in non-hepatocyte liver cells (Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells). Ageing and long-term DM1 resulted in an increased expression of TGF-β1 as well. Expression of CYP24 coexisted with the expression of TGF-β1 in all types of hepatic cells. We concluded that liver has the capacity for an active vitamin D catabolism in different populations of liver cells, especially in sinusoidal endothelial cells, through an expression of CYP24. That capacity is substantially increased during ageing and long-term diabetes mellitus. Increased liver calcitriol catabolism could be one of the mechanisms of the bone metabolism impairment related to ageing and diabetes.