Document Detail


22-Oxacalcitriol prevents progression of peritoneal fibrosis in a mouse model.
MedLine Citation:
PMID:  23032084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Vitamin D plays an important role in calcium homeostasis and is used to treat secondary hyperparathyroidism among dialysis patients. The biologic activity of vitamin D and its analogs is mediated by vitamin D receptor (VDR), which is distributed widely throughout the body. Recent papers have revealed that low vitamin D levels are correlated with severe fibrosis in chronic diseases, including cystic fibrosis and hepatitis. The aim of the present study was to evaluate the protective effects of vitamin D against the progression of peritoneal fibrosis.
METHODS: Peritoneal fibrosis was induced by injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. An analog of vitamin D, 22-oxacalcitriol (OCT), was administered subcutaneously daily from initiation of the CG injections. The peritoneal tissue was excised at 3 weeks. Changes in morphology were assessed by hematoxylin and eosin staining. Expression of VDR, alpha smooth muscle actin (as a marker of myofibroblasts), type III collagen, transforming growth factor β(TGF-β), phosphorylated Smad2/3, F4/80 (as a marker of macrophages), and monocyte chemoattractant protein-1 (MCP-1) was examined by immunohistochemistry. Southwestern histochemistry was used to detect activated nuclear factor κB (NF-κB).
RESULTS: In the CG-injected mice, immunohistochemical analysis revealed expression of VDR in mesothelial cells, myofibroblasts, and macrophages in the thickened submesothelial zone. Treatment with OCT significantly prevented peritoneal fibrosis and reduced the accumulation of type III collagen in CG-treated mice. Among the markers of fibrosis, the numbers of myofibroblasts, cells positive for TGF-β, and cells positive for phosphorylated Smad2/3 were significantly decreased in the OCT-treated group compared with the vehicle-treated group. Furthermore, OCT suppressed inflammatory mediators of fibrosis, as shown by the reduced numbers of activated NF-κB cells, macrophages, and MCP-1-expressing cells.
CONCLUSIONS: Our results indicate that OCT attenuates peritoneal fibrosis, an effect accompanied by reduced numbers of myofibroblasts, infiltrating macrophages, and TGF-β-positive cells, suggesting that vitamin D has potential as a novel therapeutic agent for preventing peritoneal sclerosis.
Authors:
Misaki Hirose; Tomoya Nishino; Yoko Obata; Masayuki Nakazawa; Yuka Nakazawa; Akira Furusu; Katsushige Abe; Masanobu Miyazaki; Takehiko Koji; Shigeru Kohno
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-02
Journal Detail:
Title:  Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis     Volume:  33     ISSN:  1718-4304     ISO Abbreviation:  Perit Dial Int     Publication Date:    2013 Mar-Apr
Date Detail:
Created Date:  2013-03-12     Completed Date:  2013-09-26     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  8904033     Medline TA:  Perit Dial Int     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  132-42     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
Calcitriol / analogs & derivatives*,  therapeutic use
Chemokine CCL2 / metabolism
Chlorhexidine / analogs & derivatives
Collagen Type III / metabolism
Disease Models, Animal
Male
Mice
Peritoneal Dialysis / adverse effects
Peritoneal Fibrosis / etiology,  pathology*,  prevention & control*
Receptors, Calcitriol / metabolism
Smad Proteins, Receptor-Regulated / metabolism
Transforming Growth Factor beta / metabolism
Vitamins / therapeutic use*
Chemical
Reg. No./Substance:
0/Actins; 0/Chemokine CCL2; 0/Collagen Type III; 0/Receptors, Calcitriol; 0/Smad Proteins, Receptor-Regulated; 0/Transforming Growth Factor beta; 0/Vitamins; 103909-75-7/maxacalcitol; FXC9231JVH/Calcitriol; MOR84MUD8E/chlorhexidine gluconate; R4KO0DY52L/Chlorhexidine
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