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


CONCLUSIONS
1α,25(OH)2D3 can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan ; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
Yi-Che
YC
Lee
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan ; School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
Shih-Yuan
SY
Hung
Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan.
Hung-Hsiang
HH
Liou
Department of Laboratory Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Tsun-Mei
TM
Lin
Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
Chu-Hung
CH
Tsai
Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
Sheng-Hsiang
SH
Lin
Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
Yau-Sheng
YS
Tsai
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Min-Yu
MY
Chang
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Hsi-Hao
HH
Wang
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan ; Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan.
Li-Chun
LC
Ho
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Yi-Ting
YT
Chen
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Ching-Fang
CF
Wu
Division of Nephrology, Department of Internal Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Ho-Ching
HC
Chen
Division of Colorectal Surgery, Department of Surgery, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Hsin-Pao
HP
Chen
Division of Colorectal Surgery, Department of Surgery, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Kuang-Wen
KW
Liu
Division of Colorectal Surgery, Department of Surgery, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Chih-I
CI
Chen
Division of Colorectal Surgery, Department of Surgery, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Kuan Min
KM
She
Department of Neurosurgery, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
Hao-Kuang
HK
Wang
Department of Medical Education, I-Shou University, Kaohsiung, Taiwan.
Chi-Wei
CW
Lin
Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan ; Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.
Yuan-Yow
YY
Chiou
D000818:Animals; D002478:Cells, Cultured; D002710:Chlorhexidine / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D056627:Peritoneal Fibrosis / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*
D014807:Vitamin D; C010882:chlorhexidine gluconate; D002710:Chlorhexidine