title: Preventive effects of vitamin D treatment on bleomycin-induced pulmonary fibrosis.
abstract: Patients with pulmonary fibrosis often have low vitamin D levels, the effects of which are largely unknown. We here report that early vitamin D supplementation significantly reduced the severity of pulmonary fibrosis and inflammatory cell accumulationin in the bleomycin-induced pulmonary fibrosis mouse model on supplementary days 14, 21 and 28 (P < 0.001). Vitamin D supplementation also prevented some ultrastructural changes in response to bleomycin administration, including basement membrane thickening, interstitial fibrin deposition and microvilli flattening or disappearance on days 14, 21 and 28, and lamellar body swelling or vacuolation on days 21 and 28. The bleomycin group had rising hydroxyproline level on days 14, 21 and 28, whereas the vitamin D treatment group showed consistently lower hydroxyproline level but still higher than that of the control group (P < 0.001). Our immunohistochemistry and densitometry analyses showed less staining for α-smooth muscle actin, a myofibroblast marker, in the vitamin D group compared to the bleomycin group (P < 0.001). Thus, vitamin D treatment could prevent bleomycin-induced pulmonary fibrosis by delaying or suppressing ultrastructural changes, as well as attenuating hydroxyproline accumulation and inhibiting myofibroblastic proliferation. These data further our understanding of the roles of vitamin D in pulmonary fibrogenesis and in the treatment of pulmonary fibrosis.
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.|Department of Pathology, Tumor Hospital of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Yunnan, 650000, China.
authors.forename: Zongmei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Aibin
authors.initials: A
authors.lastname: Liang
authors.affiliation: Electron Microscopy Core Laboratory, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Pathology, University Medical Center of Princeton at Plainsboro, Plainsboro, NJ, USA.|Department of Chemical Biology, Ernest Mario School of Pharmacy.|Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School and Piscataway, NJ, USA.|Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
authors.forename: Lanjing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yi
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000009:adverse effects* / Q000494:pharmacology; D019587:Dietary Supplements; D005337:Fibrin / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D001761:Bleomycin; D014807:Vitamin D; D005337:Fibrin; D006909:Hydroxyproline