Vitamin D can ameliorate chlorhexidine gluconate-induced peritoneal fibrosis and functional deterioration through the inhibition of epithelial-to-mesenchymal transition of mesothelial cells.

Abstract

BACKGROUND:

Peritoneal dialysis (PD) can induce fibrosis and functional alterations in PD patients' peritoneal membranes, due to long-term unphysiological dialysate exposure, partially occurring via triggering of epithelial-to-mesenchymal transition (EMT) in peritoneal mesothelial cells (MCs). Vitamin D can ameliorate these negative effects; however, the mechanism remains unexplored. Therefore, we investigated its possible links to MCs EMT inhibition.

METHODS:

Peritoneal fibrosis was established in Sprague-Dawley rats by chlorhexidine gluconate (CG) intraperitoneal injection for 21 days, with and without 1α,25(OH)2D3 treatment. Morphological and functional evaluation and western blot analysis of EMT marker were performed upon peritoneum tissue. In vitro study was also performed in a primary human peritoneal MC culture system; MCs were incubated with transforming growth factor-β1 (TGF-β1) in the absence or presence of 1α,25(OH)2D3. EMT marker expression, migration activities, and cytoskeleton redistribution of MCs were determined.

RESULTS:

1α,25(OH)2D3 ameliorated CG-induced morphological and functional deterioration in animal model, along with CG-induced upregulation of α-SMA and downregulation of E-cadherin expression. Meanwhile, 1α,25(OH)2D3 also ameliorated TGF-β1-induced decrease in E-cadherin expression, increase in Snai1 and α-SMA expression, intracellular F-actin redistribution, and migration activity in vitro.

CONCLUSION:

1α,25(OH)2D3 can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.

• Authors: Yi-Che Lee, Shih-Yuan Hung, Hung-Hsiang Liou, Tsun-Mei Lin, Chu-Hung Tsai, Sheng-Hsiang Lin, Yau-Sheng Tsai, Min-Yu Chang, Hsi-Hao Wang, Li-Chun Ho, Yi-Ting Chen, Ching-Fang Wu, Ho-Ching Chen, Hsin-Pao Chen, Kuang-Wen Liu, Chih-I Chen, Kuan Min She, Hao-Kuang Wang, Chi-Wei Lin, Yuan-Yow Chiou
• Journal: BioMed research international (Biomed Res Int) Vol. 2015 Pg. 595030 ( 2015) ISSN: 2314-6141 [Electronic] United States
• PMID: 26495304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vitamin D
• chlorhexidine gluconate
• Chlorhexidine

Topics

• Animals
• Cells, Cultured
• Chlorhexidine (analogs & derivatives)
• Dose-Response Relationship, Drug
• Epithelial-Mesenchymal Transition (drug effects)
• Epithelium (drug effects, pathology, physiopathology)
• Humans
• Male
• Peritoneal Fibrosis (chemically induced, physiopathology, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Treatment Outcome
• Vitamin D (administration & dosage)