PMID- 23032084
OWN - NLM
STAT- MEDLINE
DCOM- 20130926
LR  - 20211021
IS  - 1718-4304 (Electronic)
IS  - 0896-8608 (Print)
IS  - 0896-8608 (Linking)
VI  - 33
IP  - 2
DP  - 2013 Mar-Apr
TI  - 22-Oxacalcitriol prevents progression of peritoneal fibrosis in a mouse model.
PG  - 132-42
LID - 10.3747/pdi.2011.00234 [doi]
AB  - 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 beta(TGF-beta), 
      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 kappaB 
      (NF-kappaB). 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-beta, 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-kappaB 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-beta-positive cells, suggesting that vitamin D has 
      potential as a novel therapeutic agent for preventing peritoneal sclerosis.
FAU - Hirose, Misaki
AU  - Hirose M
AD  - Second Department of Internal Medicine, Nagasaki University School of Medicine, 
      Nagasaki, Japan.
FAU - Nishino, Tomoya
AU  - Nishino T
FAU - Obata, Yoko
AU  - Obata Y
FAU - Nakazawa, Masayuki
AU  - Nakazawa M
FAU - Nakazawa, Yuka
AU  - Nakazawa Y
FAU - Furusu, Akira
AU  - Furusu A
FAU - Abe, Katsushige
AU  - Abe K
FAU - Miyazaki, Masanobu
AU  - Miyazaki M
FAU - Koji, Takehiko
AU  - Koji T
FAU - Kohno, Shigeru
AU  - Kohno S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121002
PL  - United States
TA  - Perit Dial Int
JT  - Peritoneal dialysis international : journal of the International Society for 
      Peritoneal Dialysis
JID - 8904033
RN  - 0 (Actins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type III)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Smad Proteins, Receptor-Regulated)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Vitamins)
RN  - FXC9231JVH (Calcitriol)
RN  - MOR84MUD8E (chlorhexidine gluconate)
RN  - N2UJM5NBF6 (maxacalcitol)
RN  - R4KO0DY52L (Chlorhexidine)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Calcitriol/*analogs & derivatives/therapeutic use
MH  - Chemokine CCL2/metabolism
MH  - Chlorhexidine/analogs & derivatives
MH  - Collagen Type III/metabolism
MH  - Disease Models, Animal
MH  - Male
MH  - Mice
MH  - Peritoneal Dialysis/adverse effects
MH  - Peritoneal Fibrosis/etiology/*pathology/*prevention & control
MH  - Receptors, Calcitriol/metabolism
MH  - Smad Proteins, Receptor-Regulated/metabolism
MH  - Transforming Growth Factor beta/metabolism
MH  - Vitamins/*therapeutic use
PMC - PMC3598103
EDAT- 2012/10/04 06:00
MHDA- 2013/09/27 06:00
PMCR- 2014/03/01
CRDT- 2012/10/04 06:00
PHST- 2012/10/04 06:00 [entrez]
PHST- 2012/10/04 06:00 [pubmed]
PHST- 2013/09/27 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - pdi.2011.00234 [pii]
AID - 10.3747/pdi.2011.00234 [doi]
PST - ppublish
SO  - Perit Dial Int. 2013 Mar-Apr;33(2):132-42. doi: 10.3747/pdi.2011.00234. Epub 2012 
      Oct 2.