title: 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.
authors.affiliation: Laboratory for Neurocardiology, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Vuica
authors.affiliation: Laboratory for Neurocardiology, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia; Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vukojević
authors.affiliation: Laboratory for Pain Research, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia.
authors.forename: Lejla
authors.initials: L
authors.lastname: Ferhatović Hamzić
authors.affiliation: Laboratory for Neurocardiology, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia.
authors.forename: Milka
authors.initials: M
authors.lastname: Jerić
authors.affiliation: Laboratory for Pain Research, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia.
authors.forename: Livia
authors.initials: L
authors.lastname: Puljak
authors.affiliation: Laboratory for Neurocardiology, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia.
authors.forename: Ivica
authors.initials: I
authors.lastname: Grković
authors.affiliation: Laboratory for Neurocardiology, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia; Laboratory for Early Human Development, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Croatia. Electronic address: natalija.filipovic@mefst.hr.
authors.forename: Natalija
authors.initials: N
authors.lastname: Filipović
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000072498:Cytochrome P450 Family 24 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014807:Vitamin D / Q000378:metabolism
chemical_list: C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014807:Vitamin D; D000072498:Cytochrome P450 Family 24
keywords: Ageing; CYP24; Diabetes mellitus; Liver; TGF-β; Vitamin D