title: 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines.
abstract: Epidemiological studies showed that 1,25-Dihydroxyvitamin D[1,25(OH)2D3] insufficiency appears to be associated with aging and colon cancer while underlying biological mechanisms remain largely unknown. Inflammatory bowel disease is one of the risk factors for colon cancer. In this study, we investigated whether 1,25(OH)2D3 deficiency has an impact on the colon of 25-hydroxyvitamin D 1α-hydroxylase knockout [Cyp27b1(-/-)] mice fed on a rescue diet (high calcium, phosphate, and lactose) from weaning to 10 months of age. We found that 1,25(OH)2D3 deficient mice displayed significant colon inflammation phenotypes including shortened colon length, thinned and disordered mucosal structure, and inflammatory cell infiltration. DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were also increased significantly in the colon of Cyp27b1(-/-)mice. Furthermore, the levels of ROS in the colon were increased significantly, whereas the expression levels of antioxidative genes were down-regulated dramatically in the colon of Cyp27b1(-/-)mice. Taken together, our results demonstrated that 1,25(OH)2D3 deficiency could induce colon inflammation, which may result from increased oxidative stress and DNA damage, subsequently, induced cell senescence and overproduction of senescence-associated secretory factors. Therefore, our findings suggest that 1,25(OH)2D3 may play an important role in preventing the development and progression of colon inflammation and colon cancer.
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Zhi
authors.affiliation: Institute of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.affiliation: Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Yuan
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002117:Calcitriol; D016922:Cellular Senescence; D003092:Colitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species; D014808:Vitamin D Deficiency / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol