title: [Effects of 1, 25 (OH)2D3 on bleomycin-induced pulmonary fibrosis in mice].
abstract: OBJECTIVE
  To observe the effects of 1, 25(OH)2D3 on bleomycin-induced pulmonary fibrosis in mice and to explore its mechanisms.
  
  
  METHODS
  Ninety male C57BL/6 mice, 6 to 8 weeks old, were randomly divided into 3 groups according to the table of random numbers: a control group, a model group and a treatment group(n = 30 each). Bleomycin was injected to the mice in the latter 2 groups by single intratracheal injection to duplicate the pulmonary fibrosis model, while the control group was injected with saline. From the next day, the mice in the treatment group received 1, 25 (OH) 2D3 (0.5 µg·kg(-1)·d(-1)) diluted in olive oil by gavage daily, while the other groups were treated with equivalent olive oil. Ten mice in each group were killed randomly on day 14, 21 and 28 after surgery respectively. Pulmonary alveolitis and fibrosis were evaluated by using hematoxylin-eosin and Masson stain method. The content of hydroxyproline was measured by acid hydrolysis method. The mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4, and Wnt7a in the lung tissues were measured by real-time RT-PCR, while the protein expression of α-SMA and β-catenin were assessed by immunohistochemistry.
  
  
  RESULTS
  Pulmonary alveolitis at day 14, 21 and fibrosis at day14, 21, 28 in the treatment group were remarkably reduced compared to the model group (all P < 0.05). Compared with the model group, the treatment group showed decreased content of hydroxyproline, decreased mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4 and decreased protein expression of α-SMA and β-catenin at the 3 time points (all P < 0.05). The content of hydroxyproline and the mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4, Wnt7a in the treatment group at 28 d were 0.67 ± 0.14, 1.66 ± 0.34, 1.37 ± 0.41, 1.43 ± 0.27, 1.29 ± 0.19, 1.18 ± 0.20, respectively, all of which were significantly lower than those in the model group (1.10 ± 0.16, 3.50 ± 0.74, 2.68 ± 0.61, 2.60 ± 0.58, 2.23 ± 0.45, 1.93 ± 0.36, respectively). Protein expression of α-SMA and β-catenin in the treatment group were 0.44 ± 0.13 and 0.25 ± 0.05, respectively, which were also significantly lower than those of the model group(0.98 ± 0.20, 0.58 ± 0.06, respectively).
  
  
  CONCLUSIONS
  1, 25 (OH) 2D3 was shown to reduce pulmonary fibrosis induced by bleomycin in mice, and its mechanisms might be associated with Wnt signaling suppression.
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Zong-mei
authors: ZM
authors: Zhang
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Pan
authors: P
authors: Gu
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Email: yixhxf@163.com.
authors: Xiang-hua
authors: XH
authors: Yi
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Xia
authors: X
authors: Fang
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Yu
authors: Y
authors: Zeng
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Su-xia
authors: SX
authors: Zhang
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Xu-you
authors: XY
authors: Zhu
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Yu-dong
authors: YD
authors: Zhang
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Jun
authors: J
authors: Gu
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Wei-zhe
authors: WZ
authors: Qiu
authors: Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors: Long
authors: L
authors: Zhang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D002117:Calcitriol / Q000627:therapeutic use*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D000199:Actins; D024042:Collagen Type I; D012333:RNA, Messenger; D001761:Bleomycin; D002117:Calcitriol; D006909:Hydroxyproline