Open Access1,25(OH)2D3/VDR attenuates high glucose-induced epithelial-mesenchymal transition in human peritoneal mesothelial cells via the TGFβ/Smad3 pathway
Author(s) -
Lina Yang,
Lan Wu,
Xiuli Zhang,
Ye Hu,
Yi Fan,
Jun Ma
Publication year - 2017
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2017.6276
Subject(s) - calcitriol receptor , epithelial–mesenchymal transition , smad , mesothelial cell , cancer research , inflammation , mesenchymal stem cell , transforming growth factor , biology , endocrinology , medicine , chemistry , microbiology and biotechnology , downregulation and upregulation , immunology , vitamin d and neurology , biochemistry , pathology , gene
Epithelial-mesenchymal transition (EMT) has been recognized to accelerate peritoneal membrane dysfunction. 1,25(OH)2D3/vitamin D receptor (VDR) is important for preventing various types of EMT in vivo. However, its function on EMT and inflammation of human peritoneal mesothelial cells (HPMCs) remains to be elucidated. Therefore, the present study investigated the effects of 1,25(OH)2D3/VDR on high glucose (HG)‑induced EMT and inflammation in HPMCs and the underlying molecular mechanism. It was determined that HG reduced VDR expression, increased inflammatory cytokine expression, including transforming growth factor β (TGFβ) and interleukin‑6 (IL‑6) and phosphorylated‑SMAD family member 3 (p‑Smad3) expression. EMT was promoted as the expression level of the epithelial marker E‑cadherin was reduced, whereas expression levels of the mesenchymal markers α‑SMA and FN were increased. 1,25(OH)2D3 pretreatment inhibited the expression of inflammatory cytokines in HPMCs and attenuated HG‑induced EMT, possibly through inhibition of the TGFβ/Smad pathway by binding to its receptor VDR.